Transcript Document

Blood & Tissue Protozoa
Lange Chapter 52
Faculty: AGUAZIM SAMUEL, M.D.
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The medically important
organisms:

The sporozoans: Plasmodium and
Toxoplasma

The flagellates: Trypanosoma and
Leishmania
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Diseases caused by Trypanosoma spp. parasite
Trypanosoa
species
Vertebrate
host
vector
disease
T.bruci bruci
Horses, pigs,
cattle,
rodents
T.bruci
gambiense
Human,
Glossina spp. Sleeping
monkeys,
sikness
dogs,pigs,etc.
.
West Africa
T.bruci
rhodesiense
Human,pigs.
Glossina spp. Sleeping
sikness
East Africa
T.crusi
Human,
domestic &
wild animal.
Reduviid
bugs
(Triatoma
rhodnius)
South America
T.evansi
Glossina spp. Nagana
Epidemiolo
gy
Horses, dogs. Tabanus spp.
Chagas’
Tropical Africa
disease
Surra
India, Africa,
Australia,
South and
central
America
Trypanosoma cruzi (American
Trypansomiasis)
Disease: Chagas’ disease (American
trypanosomiasis)
Characteristics: Blood and tissue protozoan.
Life cycle:
1. Trypomastigotes in blood of reservoir host
2. Ingested by reduviid bug ( kissing bug or cone bug)
3. Form epimastigotes
4. Form trypomastigotes in the gut.
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cone-nose or kissing bug
Riduvid bug, the vector of American trypanosomiasis
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Trypanosoma cruzi
• When the bug bites, it defecates and feces containing
trypomastigotes contaminate the wound.
• Organisms enter the blood and form amastigotes within
cells; these then become trypomastigotes.
• Transmission: Transmitted by reduviid bugs. Humans and
many animals are reservoirs. Occurs in rural Latin
America.
• Pathogenesis: Amastigotes kill cells, especially cardiac
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muscle
Pathogenesis (Acute)

Acute phase
 Starts
1 week after infection
 Fever, lymph node
enlargement, unilateral
swelling of the eyelids
(Romana’s sign), acute
myocarditis, damaged
muscle cells and edema.
Pathogenesis (Chronic)

Chronic Phases:


Starts 2 months after initial
infection.
Indeterminate form: 60-70% of
people with Chagas. Completely
free of cardiac, gastrointestinal
and neurological symptoms but 25% of patients convert to cardiac
or digestive forms each year
(reason not clear).
Cardiac manifestation

Cardiac form:

30-40% of people with
Chagas. Induces
arrhythmia, cardiac failure,
thromboembolism,
atrioventricular fibrillation,
ventricular hypertrophy
Gastrointestinal manifestation

Digestive form:

10% of people. Megaoesophagus 3%,
megacolon and may be associated with
cardiac form. Difficulty in swallowing,
regurgitation, aspiration may cause
pneumonia and death. Chronic
constipation, fecal compacting causes
perforation of the colon.
Trypanosoma cruzi
Laboratory Diagnosis:
•Trypomastigotes visible in blood
•But bone marrow biopsy, culture in vitro, or serologic tests
may be required.
Clinical findings:
 facial edema (Ramana’s sign)
 nodule (chagoma) near the the bite.
 Complications include megacolon and enlarged heart.
 DEATH FROM CHRONIC CHAGAS DZ IS USUALLY DUE
TO CARDIAC ARRHYTHMIAS AND FAILURE
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Trypanosoma cruzi,
trypomastigote form,
in a blood smear
(Giemsa stain) CDC
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Chagoma: raised, non-purulent erythematous
plaque surrounded by hard edema
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Romana's sign: unilateral
conjunctivitis and orbital
edema
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Trypanosoma cruzi
Treatment: Nifurtimox and benznidazole
for
acute disease. No effective drug for chronic disease.
Prevention: Protection from bite. Insect control.
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Trypanosoma
Disease: Sleeping sickness (African trypanosomiasis)
•Trypanosomiasis is a systemic disease caused by the
parasite Trypanosoma brucei.
• East African trypanosomiasis: T. rhodesiense
• West African trypanosomiasis: T. gambiense.
• It is transmitted by the bite of the tsetse fly, a graybrown insect about the size of a honeybee.
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Trypanosoma (African Sleeping Sickness)
Characteristics: Blood and tissue protozoan.
Life cycle:
1. Trypomastigotes in blood of human or animal
reservoir, are ingested by tsetse fly.
3. They differentiate in the gut to form epimastigotes
4. Metacyclic trypomastigotes formed in salivary glands.
5. When fly bites, trypomastigotes enter the blood.
6. Repeated variation of surface antigen occurs, which
allows the organism to evade the immune response.
Recurrent Fever.
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MOT: metacyclic
trypomastigote
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Tsetse fly. The vector of African trypanosomiasis
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Trypanosoma (African Sleeping Sickness)
Transmission: Transmitted by tsetse flies.
Pathogenesis:
encephalitis.
Trypomastigotes
infect
brain,
causing
Laboratory Diagnosis:
Trypomastigotes visible in blood in early stages and in
cerebrospinal fluid in late stages.
Serologic tests useful.
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METACYCLIC TRYPOMASTIGOTE
Blood smear from a patient (a U.S. traveler) with Trypanosoma
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Pathogenesis (2 stages)

Stage 1: Haemolymphatic
stage (ACUTE)





Most patients do not notice this
stage of infection.
Small papule from bite may develop
exciting local inflammation.
When trypomastigotes enter the
haemo-lymphatic system to
multiply,clinical symptoms include:
Fever, headache and joint pain
Winterbottom’s sign: swelling of
lymph nodes at the posterior neck
region.

Stage 2: Meningoencephaltic
stage (CHRONIC)
 Sleeping
sickness stage because
trypanosomes have crossed the
blood-brain barrier
 Personality changes, headaches
and withdrawal from the
environment.
 Simple tasks become harder to
accomplish as individual
experience nocturnal insomnia
and daytime lethargy, apathy and
ultimately succumb to secondary
infections such as pneumonia.
Trypanosoma African Sleeping Sickness
Clinical Finding: Important!!!

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Indurated skin ulcer (trypanosomal chancre) at the
site of fly bite
Fever for 1 wk./ no fever 2 wks./fever again
Enlargement of the glands of the posterior cervical
region (Winterbottom's sign)
Neurological complications can occur as a result of
infection.
Wasting and skin damage caused as a result of the
intense itching which can accompany late-stage
disease.
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Coma
The leg of a teenage girl who has sleeping sickness, showing the chancre
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at the site of the tsetse fly bite
Parasitemia
2-3 WEEKS after the bite
fever
malaise, lassitude
insomnia, headache
lymphadenopathy and edema
 Kerandel's sign : painful sensitivity of
palms and ulnar region to pressure
 Febrile episodes:
few months- Rhodesian disease
several years - Gambian disease

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Very characteristic of Gambian
disease is visible enlargement of the
glands of the posterior cervical region
(Winterbottom's sign)
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CNS Stage

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changes in character and personality
lack of interest and disinclination to work
avoidance of acquaintances
morose and melancholic attitude alternating with
exaltation
mental retardation and lethargy
low and tremulous speech
tremors of tongue and limbs
slow and shuffling gait
altered reflexes
males become impotent
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Neuropathology of Human African Trypanosomiasis
Acute hemorrhagic leucoencephalopathy
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Why do they call it sleeping
sickness?
DAYTIME SOMNOLENCE
NIGHTTIME INSOMNIA
Micro class
Ziggy’s
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DOC:
 1. Pentamidine–inhibiting dihydrofolate
reductase enzyme, interfering with aerobic
glycolysis
 2. Suramin – trypanocidal; inhibiting
parasitic enzymes ,growth factors
 3. Melarsoprol – CNS; trypanocidal,
inhibiting parasitic glycolysis ; late disease

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PREVENTION
Protection against the fly bite, using netting and
protective clothing.
 Clearing forest around villages
 Irradiation of male flies technique
 Chemical sprays( insecticides)

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LEISHMANIASIS
Introduction

In the Middle East L. major and L. tropica are the
most common species
•
•
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
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L. major causes skin infection
L. tropica causes skin and visceral infection and rarely
causes mucocutaneous infection
About 1.5 million new cases of cutaneous
leishmaniasis in the world each year
500,000 new cases of visceral leishmaniasis
estimated to occur each year also
20 cases of cutaneous leishmaniasis from L. major/
L tropica and twelve cases of visceral infection
caused by L. tropica were reported in soldiers from
Desert Storm
Endemic Areas for Leishmaniasis
BMJ 2003;326:378
Leishmaniasis in the Middle East


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90% of cutaneous leishmaniasis occurs in Afghanistan, Iran, Saudi Arabia,
Syria, Brazil and Peru
• 8,779 cases were reported in Iraq in 1992
• Sore is commonly called the Baghdad boil
• At least 20 cases of cutaneous leishmaniasis were reported in
Americans from Desert Storm
90% of all visceral leishmaniasis occurs in Bangladesh, Brazil, India, and the
Sudan
• 2893 cases were reported in Iraq in 2001
• 12 visceral leish cases were reported in Americans in Desert Storm
90% of mucocutaneous leishmaniasis occurs in Bolivia, Brazil and Peru
• Rarely associated with L tropica which is found in Middle East
LEISHMANIASIS:


Leishmania
2nd largest parasitic killer in the world

L. donovani: visceral leishmaniasis
(Kala-azar, black disease, dumdum fever)

L. tropica: cutaneous leishmaniasis
(oriental sore, Delhi ulcer, Aleppo, Delhi or Baghdad boil)

L. braziliensis: mucocutaneous leishmaniasis (espundia, Uta,
chiclero ulcer)
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LEISHMANIASIS
prevalent world wide
 south east Asia
 Indo-Pakistan
 Mediterranean
 north and central Africa
 south and central America

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MOT: bite of Sandfly (Phlebotomus)
aka sandflea, no-see-um, no-see-em, noseeum,
sand gnats, chitras, punkie, or punky
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Infective form: promastigote
Intracellular form: amastigote
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Leishmania donovani
Disease: Kala-azar
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Leishmania donovani
Characteristics: Blood and tissue protozoan
Life cycle:
1. Human macrophages containing amastigotes are ingested
by sandfly.
2. Amastigotes differentiate in fly gut to promastigotes
3. Migrate to pharynx which can be transmitted during next
bite.
4. When fly bites, promastigotes enter blood and engulfed by
macrophages and form amastigotes.
5. These can infect other reticuloendothelial cells, especially
in spleen and liver.
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Leishmania donovani
Transmission:
•Transmitted by sandflies.
• Animal reservoir (chiefly dogs, small carnivores,
and rodents) in Africa, Middle East, and parts of
China.
•Human reservoir in India.
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Leishmania donovani
Pathogenesis:
Amastigotes
kill
reticuloendothelial cells, especially in liver,
spleen, and bone marrow.
Laboratory Diagnosis:
• Amastigotes visible in bone marrow smear
• Serologic tests useful.
• Skin test indicates prior infection.
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Leishmania donovani
Clinical Finding:
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Severe muscle wasting.
visceral leishmaniasis develop a noticeable thickening,
stiffening and darkening of the eyelashes and eyebrows
Jaundice
Enlarged spleen and liver
Skin ulcer
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Profile view of a teenage boy
suffering
from
visceral
leishmaniasis(dumdum fever). The
boy
exhibits
splenomegaly,
distended abdomen and severe
muscle wasting. CDC
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Many children suffering from visceral leishmaniasis develop a noticeable
thickening, stiffening and darkening of the eyelashes and eyebrows
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
A 12-year-old boy
suffering from visceral
leishmaniasis. The
boy exhibits
splenomegaly and
severe muscle
wasting.
Jaundiced hands of a visceral leishmaniasis patient
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
Enlarged spleen and
liver in an autopsy of
an infant dying of
visceral leishmaniasis.
Skin ulcer due to leishmaniasis, hand of Central American adult. CDC
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Cutaneous leishmaniasis
(Oriental sore, Delhi ulcer, Baghdad boil)


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L. tropica
multiplies locally
encrusted ulcer with
satellite papules
disfiguring scar
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Cutaneous Leishmaniasis
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Most common form
Characterized by one or more sores, papules or
nodules on the skin
Sores can change in size and appearance over
time
Often described as looking somewhat like a
volcano with a raised edge and central crater
Sores are usually painless but can become
painful if secondarily infected
Swollen lymph nodes may be present near the
sores (under the arm if the sores are on the arm
or hand…)
Cutaneous Leishmaniasis

Most sores develop within a few weeks of the sandfly bite,
however they can appear up to months later

Skin sores of cutaneous leishmaniasis can heal on their
own, but this can take months or even years

Sores can leave significant scars and be disfiguring if they
occur on the face

If infection is from L. tropica it can spread to contiguous
mucous membranes (upper lip to nose)
Cutaneous leishmaniasis of
the face.
A cutaneous leishmaniasis
lesion on the arm.
Scar on skin of upper leg representing healed lesion of leishmaniasis CDC
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Girl with diffuse cutaneous leishmaniasis of the face which is responding to treatment
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Mucocutaneous Leishmaniasis
L. braziliensis
begins with a papule at the bite
site, but then metastatic lesions
form, usually
at the mucocutaneous junction of
the nose and
mouth.
Disfiguring granulomatous,
ulcerating lesions destroy nasal
cartilage but not adjacent hone.
These lesions heal slowly, if at all.
Death can occur from secondary
infection.
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Treatment and Prevention
DOC: Sodium stibogluconate
-potent inhibitor of parasitic enzymes
,enhancer of cytokines
 Amphotericin B: resistant strains

PREVENTION
 Protection from sandflies using netting,
protective clothing and insect repellents
and insecticide spraying.

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The
Highest form of Deception is
to Think or Believe….Everybody is
Doing It!!!!!!
General Bison
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