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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CASE

40 year old male on a business trip to WEST AFRICA
presented with sudden fever, joints pains and headache
which were most severe every 3rd day. In between, he would
fell weak, but the fever would lyse.

He had vaccine for yellow fever and HAVRIX prior to leaving
the US.

He was staying in a urban hotel, and had limited trips except
for the office.
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CASE

Thick blood smear showed:
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CASE

Impression: Malaria, probably nonChloroquine resistant; secondary to
Plasmodium species
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It was discovered
more than 100 years ago
A French army doctor in
Algeria observed
parasites inside red blood
cells of malaria patients
and proposed for the first
time that a protozoan
caused disease
Charles Louis Alphonse Laveran
www.uhhg.org/mcrh/resources/video/malariappt.pdf
1907 Nobel Prize for Physiology
or Medicine!
French army doctor in
Algeria observed
parasites inside red blood
cells of malaria patients
and proposed for the first
time that a protozoan
caused disease
Charles Louis Alphonse Laveran
www.uhhg.org/mcrh/resources/video/malariappt.pdf
PLASMODIUM
 Disease: Malaria

Malaria is caused by four plasmodia: vivax,
ovale, malariae, and falciparum.

Vivax and falciparum are more common
causes of malaria than are ovale and
malariae.
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Malaria
300–500 million infections worldwide and
approximately 1 million deaths annually.
•
• 10 million new cases
• more than 2 million die of it each year,
making it the most common lethal infectious
disease.
•http://www.cdc.gov/travel/other/malaria_dr_2004.htm
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Important Properties of Malaria
• The vector and definitive host for plasmodia is
the female Anopheles mosquito (only the
female takes a blood meal).
There are two phases in the life cycle:

Sexual cycle,
mosquitoes.
which
occurs
primarily
in

Asexual cycle, which occurs in humans the
intermediate hosts.
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13. Fertilization
14. Invasion of gut mucosa
15. Oocyte
16. Sporozoite
17. Released into gut
Sexual
18. Salavary glands
Asexual
1. Sporozoite
2. Parenchymal cells of the liver.
4. Mature in two weeks into schizonts.
5. Rupture to produce 10-40,000
merozoites.
6. Circulate for a few minutes before
entering the red blood cell.
7. Merozoites mature into the ring
form in the RBC.
8. From ring form to Trophozoite.
9. From Trophozoite to Schizont.
10. Completion of life cycle to release
merozoites into the blood stream.
11. Some merozoites initiate the
sexual stage to form male and
female gametocytes.
12. Gametocytes taken up by the
Anophles mosquito; eight male
microgametes
and
female
macrogametes are produced in
the gut.
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12
Mosquito feeds on blood of infected
host & ingests gametocytes
13
Gametes unite in mosquito
stomach to form oocysts in wall of
stomach
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Oocysts
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16
Sporozoites produced in oocysts by
sporogony move to salivary glands of
mosquito & are injected into next host
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Sporozoites invade liver cells and
undergo schizogony to produce
merozoites
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Merozoites invade circulating
RBCs
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Each merozoite produces as
many as 36 new merozoites
through schizogony in RBCs
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Merozoites rupture RBCs to
invade other RBCs
Simultaneous lysing of RBCs causes the
sudden chills & fever typical of malaria
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Gametocytes are produced in
blood & ingested by mosquito to
complete the cycle
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Man
Mosquito
Sporozoites from mosquito bite
Ingest gametocytes
Sporozoites to liver
Fertilization in stomach
Schizogony to make merozoites
Oocyst forms
Merozoites enter RBCs
Sporozoites by sporogony
Schizogony to make merozoites
Sporozoites invade salivary gland
Merozoites
Merozoitesbecome
becomegametocytes
gametocytes
Bites man
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Plasmodium falciparum merozoites ring form.
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Pathogenesis of Malaria:
• Most of the pathologic findings of malaria result from
the destruction of red blood cells.
• Red cells are destroyed both by the release of the
merozoites and by the action of the spleen.
• Malaria caused by P falciparum is more severe
than that caused by other plasmodia.
• It is characterized by infection of far more red cells
than the other malarial species.
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Malaria Clinical Findings
Abrupt onset of fever, chills and Headache
Myalgias, about 2 weeks after the mosquito bite.
 Fever may be continuous early in the disease
 Untreated malaria caused by P. falciparum is potentially life-threatening
as a result of extensive brain and kidney damage.
 Malaria caused by the other three plasmodia is usually self-limited, with a
low mortality rate.
life-threatening hemorrhage and necrosis, particularly in the brain (cerebral
malaria).
Extensive hemolysis and kidney damage occur, with resulting hemoglobinuria.
The dark color of the patient’s urine has given rise to the term “blackwater
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fever.”
Malaria Clinical Differences between species:
•P. falciparum causes a high level of parasitemia,
because it can infect red cells of all ages.
•P vivax infects only reticulocytes.
•P malariae infects only mature red cells; they
produce much lower levels of parasites in the
blood.
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SPECIES
DISEASE
IMP:FEAT
URES
BLOOD
SMEARS
LIVER
STAGES
TRT
P.VIVAX
BENIGN
TERTIAN
48HRS
FEVER
SPIKES
Enlarge host
cells,
schuffner’s
dots ameboid
trophozoites
Persistent
hypnozoites
relapse
Chloroquine
then
primaquine(
needed to
eliminate the
exoerythrocytic
form)
p. ovale
““
“”
Oval, jagged,
infected RBC
“”
“”
P .malariae
Quartan or 72hrs
malarial
fever
spikes,
recrudesc
ence
Bars and band
forms, rosette
schizonts
No
persistent,
Recrudesce
nce
chloroquine
Multiple
ringforms,
crescent shape
gametes
“”
Chloroquine
resistance a
problem
P .falciparum Malignant
tertian
Irregular
fever
spikes,
cerebral
malaria
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Bars and band forms,
schuffner’s dots
Multiple ringforms,
Oval, jagged, infected RBC
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Sickle Cell Anemia and Malaria
•Individuals with sickle cell trait are protected
against malaria
• Their red cells have too little ATPase activity
and cannot produce sufficient energy to support
the growth of the parasite.
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Malaria and the Duffy antigen
•The receptor for P vivax is the Duffy blood
group antigen.
•People who are homozygous recessive for the genes
that encode this protein are resistant to infection by
P. vivax.
•More than 90% of black West Africans and many
of their American descendants do not produce the
Duffy antigen.
Homozygous: having identical genes at one or more loci
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Malaria is transmitted primarily by mosquito bites,
but transmission can occur:
• across the placenta
• in blood transfusions
• intravenous drug abuse also occur.
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Laboratory Diagnosis of Malaria:
•Diagnosis rests on microscopic examination of blood,
using both thick and thin Giemsa-stained smears.
- thick smear: used to screen for the presence of
organisms
- thin smear is used for species identification.
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It is important to identify the species, because
the treatment of different species can differ.
•Ring shaped trophozoites can be seen within
infected red blood cells.
•The gametocytes of P. falciparum are crescent
shaped (banana-shaped)
• The gametocytes of the other plasmodia are
spherical.
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P falciparum female gametocyte banana-shaped
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Treatment of Malaria:
http://www.artemisininproject.org/Current_Treatments
Chloroquine:acute malaria: (kills the merozoites) reducing
the parasitemia. Check CDC for Chloroquine resistant
areas!!!
•Dose, 500 mg. orally per week for one week prior to travel,
during travel and 4 week afterwards.
•Chloroquine prophylaxis only effective for travelers to
malaria-risk areas in:
- Mexico
-Central America
- Haiti
-Middle East
- Dominican Republic -Eastern Europe 37
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Other Malaria Treatments

For chloroquine resistant strains of P falciparum: mefloquine,
doxycycline or a combination of quinine and Fansidar is used.
Neurologic side effects such as psychosis for Mefloquine.

Primaquine or Pyrimethamine: is used to treat the hypnozoites
of P vivax and P ovale in the liver. Primaquine must be used to
prevent relapses.

Malarone: new drug: combination of atovaquone and
proguanil. First dose 1-3 days before travel, during travel and 7
days after travel. Can’t use in pregnant women, breast-feeding
women and infants< 24 lbs.
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Prevention of Malaria: Chemoprophylaxis
•Travelers to areas where the plasmodia are found should take
chloroquine starting 1-2 weeks before arrival and continuing for 4-6
weeks after departure.
•Travelers to areas where chloroquine resistant P falciparum is endemic
consists of mefloquine. This should be followed by a 2-week course of
primaquine if exposure was high.
• use of mosquito netting, window screens, protective clothing, and
insect repellents.
•The mosquitoes feed from dusk to dawn, so protection is particularly
important during the night.
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Although….
www.columbia.edu/itc/hs/medical/pathophys/parasitology/2006/PAR-05Color .pdf
Babesia








Babesiosis: fever and hemolytic
anemia(malaria-like)
Predominantly in the northeastern
U.S.
Co-infection with borrelia
Blood smear, no RBC pigment
Appears as a “Maltese
cross”(tetrad in RBCs)
MOT: TICK BITE(ixodes tick)
hemolytic anemia, jaundice, fever
and hepatomegaly, usually 1-2
weeks after infection
DOC:atovaquone and azithromycin (mildto-moderate cases) or clindamycin and
quinine (severe or resistant cases).
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Acanthamoeba castellanii (FREELIVING AMEBA)









"the brain-eating amoeba“
Rapidly fatal meningoencephalitis
( granulomatous amebic encephalitis)
Thought to be acquired via respiratory route and via breaks in
the skin
Their life cycle involves trophozoite and cyst stages. Cysts are
quite resistant and are not killed by chlorination
Free living amebae in contaminated and contact lens
solution(airborne-cyst)
DX: Amoebas in spinal fluid
Pentamidine, ketoconazole, or flucytosine may be effective in
Acanthamoeba infections
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ACANTHAMOEBA ALSO CAUSES KERATITIS
Naegleria fowleri
(FREE-LIVING AMEBA)








"the brain-eating amoeba“
Rapidly fatal meningoencephalitis
( primary amebic meningoencephalis), severe frontal
headache, nausea, high fever. Altered sense of smell (
often fatal)
Swimming in freshwater lakes
Their life cycle involves trophozoite and cyst stages. Cysts are
quite resistant and are not killed by chlorination
Enters via the cribriform plate
DX: Amoebas in spinal fluid
AMP B MAY BE EFFECTIVE FOR NAEGLERIA
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Tissue Protozoa
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Toxoplasma gondii
Disease: Toxoplasmosis
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WHAT IS TOXOPLASMOSIS?
Toxoplasmosis is an infection caused by a parasite most
often found in cats and farm animals. Humans can catch
this disease from:
coming into contact with infected cat feces
eating raw or undercooked meat that’s infected
eating contaminated vegetables or fruits
being born with it
Note: Once a person is infected, the infection remains in
the body for life, usually in an inactive form. It can
reactivate when that person’s immune system is weak.
Epidemiology


More than 60 million people in the
United States probably carry the
Toxoplasma parasite, but very few
have symptoms because the
immune system usually keeps the
parasite from causing illness.
However, expectant mothers
should be cautious because an
infection can cause problems in
pregnancy.
Image pictured is of brain tissue
with abnormal growth due to
toxoplasmosis
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About 98% of cases of Toxoplasmosis are
acquired through Congenital Toxoplasmosis.
One study showed that 76% of
infants infected with congenital
toxoplasmosis had ocular lesions,
51% had neurological involvement,
and 26% had either hydrocephalus
(increased intracranial pressure) or
michrocephaly (small brain). It is
evident that vision problems are
very common with Congenital
Toxoplasmosis.
Once the mother develops
immunity to the organism, all
future pregnancies are protected
from transmission of the organism.
Toxoplasma Characteristics:
• Tissue protozoan.
Life cycle in human:
1. Cysts in cat feces or meat
2. Ingested by humans
3. Differentiate in the gut and invade
4. Infect macrophages
5. Form trophozoites (tachyzoites) that multiply,
kill cells, and infect other cells
6. Cysts containing bradyzoites form later in the
host cell, brain, muscle, and other tissues!!!!!!
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Infective form: oocysts
Pathogenic form: tachyzoite
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Toxoplasma Life cycle in cat:
1. Cat ingests cysts in raw meat
2. Bradyzoites released from the cyst in the small
intestine.
3. Multiply, and form gametocytes.
4. These fuse to form oocysts in cat gut, which are
excreted in cat feces.
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Toxoplasma
Human infection: usually occurs from eating
undercooked meat lamb or pork, from animals
that grazed in soil contaminated with infected cat
feces.
Transmission: Transmitted by ingestion of cysts
and transplacentally from mother to fetus. Cat is
definitive host; humans and other mammals are
intermediate hosts. Occurs worldwide.
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CONGENITAL
TOXOPLASMOSIS

classic clinical triad


retinochoroiditis

cerebral calcifications


convulsion


TORCH
T – Toxoplasmosis
O – Others (VSZ and
Parvovirus B19
R – Rubella
C – CMV
HE – Herpes, HIV
S – Syphilis
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3. Children born with Toxoplasmosis, which accounts for
about 98% of cases, may show symptoms including:













Fever
Swollen glands
Jaundice
An unusually large or small head
Rash
Bruises or bleeding under the skin
Anemia
Enlarged liver or spleen
Seizures
Limp muscle tone
Mental retardation
Hearing loss
Vision problems (toxoplasmosis of the eye)
TOXOPLASMOSIS
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Ocular toxoplasmosis:
Macular scarring
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DAMAGE TO THE EYE
The parasite usually invades the retina and the choroid tissue.
Depending upon the area and severity of the infection, visual
acuity can be unaffected to severely affected. The retina is
inflamed by the infection and sometimes when the inflammation
settles, scars are left on the retina. Symptoms include floaters
and blurred vision. If the scarring is on the central macula,
detailed vision will be affected. Approximately 35% of all
retinachoroiditis cases can be attributed to toxoplasmosis.
Active Toxoplasmosis
Inactive Toxoplasmosis Scar
Effects of Ocular Toxoplasmosis
Common Effects:
Occasional Effects:
 Inflammation
of
retina
 Blurred vision
 Floaters
 Nystagmus
 Amblyopia
 Squint
 Cataracts
 The
eye can be small
 Optic atrophy
 Cerebral visual
impairment
Toxoplasma
Pathogenesis: Trophozoites infect many organs,
especially brain, eyes, and liver. Cysts persist in
tissue.
Laboratory Diagnosis: Serologic tests for IgM and IgG
antibodies are usually used.
Treatment: Sulfonamide and pyrimethamine for
congenital or disseminated disease.
Prevention: Meat should be cooked. Pregnant women
should not handle cats, cat litter boxes, or raw
meat.
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Classic Triad of
Congenital toxoplasmosis
Chorioretinitis ( Cotton-like white/yellow
scars on the retina)
 Hydrocephalus
 Intracranial calcification( multiple ringenhancing lesions in the cortex and basal
ganglia on head CT)

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Ring Enhancing lesion
Toxoplasmosis
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Thank You!!!!
 In
the Race of Life Overtaking
is Permitted. Remember Life is
a Privilege not a right. DRS
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