Transcript BLOOD AND TISSUE PROTOZOA-2

BLOOD AND TISSUE
PROTOZOONS
PLASMODIUM
TRYPANASOMA
BABESIA
Doç.Dr.Hrisi BAHAR
PLASMODIUMS
PLASMODIUM SPECIES CAUSES
“MALARIAS”
Plasmodium
falciparum
IN HUMAN
Plasmodium vivax
Plasmodium
malariae
►Plasmodium
falciparum
►Plasmodium
vivax
Plasmodium
ovale
►Plasmodium malariae
►Plasmodium ovale
PLASMODIUMS
►The malaria parasite exhibits a complex life
cycle involving an insect vector (mosquito) and
a vertebrate host (human).
► Four Plasmodium species infect humans.
► All four species exhibit a similar life cycle with
only minor variations.
PLASMODIUMS
1*The infection is initiated when
sporozoites are injected with the saliva of
a feeding mosquito.
Sporozoites are carried by the circulatory
system to the liver and invade hepatocytes
2*The intracellular parasite undergoes an
asexual replication known as
exoerythrocytic schizogony within the
hepatocyte
PLASMODIUMS
3*Exoerythrocytic schizogony activates the
production of merozoites which are released
into the bloodstream
4*Merozoites invade erythrocytes and undergo a
trophic period in which the parasite enlarges
5*The early trophozoite is often referred to as
'ring form' because of its morphology.
PLASMODIUM
Ring form
Ring form
Plasmodium vivax
Plasmodium malaria
Scanning electron micrograph of
Plasmodium-infected red blood cells.
One cell has burst open, releasing
merozoites
PLASMODIUM
► Trophozoite enlargement is accompanied
by an active metabolism including the
ingestion of host cytoplasm and the
proteolysis of hemoglobin into amino acids.
► The end of the trophic period is manifested
by multiple rounds of nuclear division
without cytokinesis resulting a schizont
PLASMODIUM
► A proportion of the liver-stage parasites
from P. vivax and P. ovale go through a dormant
period instead of immediately undergoing
asexual replication
► These hypnozoites will reactivate several
weeks to months (or years) after the primary
infection and are responsible for relapses.
PLASMODIUM
► The merozoites from the mature schizont
are released following rupture of the
infected erythrocyte.
► Invasion of erythrocytes reinitiates another
round of the blood-stage replicative cycle
Life cycle
Life cycle
PLASMODIUM
► The blood stage is responsible for the
pathology associated with malaria
► The intermittent fever paroxyms are
due to the synchronous lysis of the
infected erythrocytes
PLASMODIUM
► P.malariae exhibits a 72 hour periodicity,
whereas the other three species exhibit 48
hour cycles for the fever.
►P. falciparum often exhibits a continuous
fever rather than the periodic paroxyms.
P.falciparum also is responsible for more
morbidity and mortality than the other
species
PLASMODIUM
► This increase virulence is due in part to the
higher levels of parasitemia associated with
P. falciparum infections. In addition, more
complications are associated with P.
falciparum because of the sequestration of
the trophozoite- and schizont-infected
erythrocytes in the deep tissues
PLASMODIUM
► As an alternative to the asexual replicative cycle,
the parasite can differentiate into sexual forms
known as macro- or microgametocytes
► The gametocytes are large parasites which fill up
the erythrocyte, but only contain one nucleus.
► Ingestionof gametocytes by the mosquito vector
induces gametogenesis and escape from the host
Erythrocyte.
PLASMODIUM
►Microgametes, formed by a process
known as exflagellation , are flagellated forms
which will fertilize the macrogamete
leading to a zygote .
► The zygote develops into a motile ookinete
which penetrates the gut epithelial cells and
develops into an oocyst
PLASMODIUM
► The oocyst undergoes multiple rounds of
asexual replication resulting in the
production of sporozoites .
► Rupture of the mature oocyst releases
the sporozoites into the body cavity of
the mosquito The sporozoites migrate to
and invade the salivary glands, thus
completing the life cycle.
PLASMODIUM
In summary, malaria parasites undergo
three distinct asexual replicative stages
1-Exoerythrocytic schizogony
2-Blood stage schizogony
3- Sporogony
General Clinical Manifestation
of “Malaria”
► Infection is characterized by acute febrile
attacks (malaria paroxysms) due to blood
stage (not liver stage or gametocytes)
► Manifestations and severity of the
infection depend on species and host
status, immunity, general health,nutritional
state, genetics.
General Clinical Manifestation
of “Malaria”
► Recrudescences or relapses can occur
over months or years and can develop
severe complications.(especially P.
falciparum)
PATHOGENESIS OF
“MALARIA”
Primary attack
► Infected erythrocyte rupture 
products of schizont, stimulate the release
of cytokines (TNF)  paroxysm (shiver,
fever, sweat)
PATHOGENESIS OF
“MALARIA
Relapse
► It is a recurrence that taken place after
complete initial clearing of the erythrocytic
infection and implies reinvation of the
blood stream by merozoites from activated
hypnozoites in liver.
PATHOGENESIS OF
“MALARIA
Recrudescence
► It is a recurrence of symptoms in a patient
whose blood stream infection has previously
been at such a low level as not to be clinically
demonstrable or cause symptoms.
Complications Of “MALARİA”
► Anemia
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Hemolysis of infected erythrocytes
Hypersplenism
Autoimmunization of uninfected erythrocytes
TNF-
► Splenomegaly:
► Malarious nephrosis
► Cerebral malaria
Diagnosis of “Malaria”
► 1.Parasite; Species; Density
*Thin blood films (species identification)
*Thick blood films
Diagnosis of “Malaria”
► 2 Immuno-diagnosis
*Specific antibody detection
*Antigen detection
*Specific DNA or RNA detection
Treatment
1. Treatment by classes of antimalarial drugs
► 1) Blood schizonticides (quinine; chloroquine;
artemisinin; mefloquine; sulfadoxinpyrimethamine)
-Effect on erythrocytic stage, use for acute
attack.
Treatment
► 2) Tissue schizonticides (Primaquine)
-Effect on the stages in liver (including
hypnozoite), use for prevent relapse (radical
cure) of P.v or P.o malaria
Choice of drugs
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1) Treatment of vivax, malariae, ovale and
chloroquine-sensitive falciparum malaria:
chloroquine
2) Radical cure of vivax or ovale malaria:
chloroquine + primaquine
3) Treatment of chloriquine-resistant
falciparum malaria: artemisinin or mefloquine
or quinine
Transmission and prevention
► Factors of transmission
Suitable species of anopheles (60
species are considered to be vectors
of malaria, major vectors in China:
A. sinensis, A. minimus)
Transmission and prevention
Prevention:
Breaking the human-mosquito-human cycle
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1) Control of the source of infection by
chemotherapy
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2) Control of transmission route:
residual insecticides, avoidance of infected
mosquitoes
Transmission and prevention
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3) Chemoproplylaxis
Taking suppressive drugs, beginning one
week before travel to endemic area and
continuing until 6 weeks after return
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4) Malaria vaccines
TRYPANASOMA
► Trypanosomes infect a variety of hosts
and cause various diseases, including the
fatal disease SLEEPING SICNESS in
humans. These deadly parasites mostly
live in the blood and tissue fluids but can
also inhabit intracellular locations in the
host's body as well.
“Trypanasoma”
Life cycle
► < Infection occurs when infected
metacyclic trypomastigotes enter the body
through wound openings or mucous
membranes.
► < The trypomatigotes enter various cells,
differentiate into amastigotes and multiply
intracellularly.
Life cycle
► < The amastigotes differentiate into
trypomastigotes which are then released
back into the bloodstream.
► < The life cycle is continued when a
reduviid bug feeds on an infected person
and ingests trypomastigotes in the blood
meal.
Life cycle
TRYPANASOMA
► Human African Trypanosomiasis, also
known as sleeping sickness, is a vectorborne parasitic disease.
► The parasites concerned are protozoa
belonging to the Trypanosoma Genus.
► They are transmitted to humans by
tsetse fly (Glossina Genus) bites which
have acquired their infection from human
beings or from animals harbouring the
human pathogenic parasites.
tsetse fly
Glossina brevipalpis
TRYPANASOMA
► Sleeping sickness occurs only in subSaharanAfrica in regions where there are
tsetse flies thatcan transmit the disease.
► For reasons that are so far unexplained,
there are many regions where tsetse flies
are found, but sleeping sickness is not.
TRYPANASOMA
► Sleeping sickness generally occurs in remote
rural areas where health systems are weak or
non-existent. The disease spreads in poor
settings. Displacement of populations, war and
poverty are important factors leading to
increased transmission.
► The disease develops in areas whose size can
range from a village to an entire region. Within a
given area, the intensity of the disease can vary
from one village to the next
TRYPANASOMA
Human African Trypanosomiasis takes two forms,
depending on the parasite involved.
1.form
► Trypanosoma brucei gambiense (T.b.g.) is found in
west and central Africa. This form represents more than
90% of reported cases of sleeping sickness and causes
a chronic infection.
► A person can be infected for months or even years
without major signs or symptoms of the disease. When
symptoms do emerge, the patient is often already in an
advanced disease stage when the central nervous
system is affected.
TRYPANASOMA
2.Form
► Trypanosoma brucei rhodesiense (T.b.r.) is
found in eastern and southern Africa. This form
represents less than 10% of reported cases and
causes an acute infection.
First signs and symptoms are observed after a
few months or weeks. The disease develops
rapidly and invades the central nervous system.
TRYPANASOMA
Another form of trypanosomiasis occurs in
15 Central and South American countries.
It is known as :
American Trypanosomiasis or “Chagas
disease”. The causal organism is a
different species from those causing the
African form of the disease.
Symptoms of
“Sleeping Sicness”
The disease is transmitted through the bite of
an infected tsetse fly. At first the trypanosomes
multiply in subcutaneous tissues, blood and
lymph. In time, the parasites cross the bloodbrain barrier to infect the central nervous
system. The process can take years.
Symptoms of
“Sleeping Sicness”
► The first stage of the disease, known as a
“haemolymphatic phase”, entails bouts of
fever, headaches, joint pains and itching.
► The second stage, known as the
“neurological phase”, begins when the
parasite crosses the blood-brain barrier
and invades the central nervous system .
Symptoms of
“Sleeping Sicness
► In general this is when the signs and symptoms
of the disease appear: confusion, sensory
disturbances and poor coordination. Disturbance
of the sleep cycle, which gives the disease its
name, is an important feature of the second
stage of the disease.
► Without treatment, sleeping sickness is fatal.
Diagnosis
Diagnosis must be made as early as
possible and before the neurological stage
in order to avoid complicated, difficult and
risky treatment procedures.
Diagnosis follows a three-step pathway
► Screening
► Diagnostic confirmation,
► Staging.
Diagnosis
► ► Diagnostic confirmation then relies on
the finding of trypanosomes in the blood,
lymph nodes, or cerebrospinal fluid (CSF).
Unfortunately, it is estimated that 20 to
30% of patients are missed by the
standard parasitological techniques
Treatment
First stage treatments
 Pentamidine: discovered in 1941, used
for the treatment of the first stage of T.b.
gambiense sleeping sickness.
 Suramin: discovered in 1921, used for the
treatment of the first stage of T.b.
rhodesiense.
Treatment
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Second stage treatments
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Melarsoprol: discovered in 1949, it is
used in both forms of infection.
Eflornithine: this molecule, less toxic
than melarsoprol, was registered in
1990. It is only effective against T.b.
gambiense.
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BABESIA
► Babesia is a protozoan parasite of the
blood that causes a hemolytic disease
known as Babesiosis.
► Babesia microti and Babesia
divergens are the two species to most
frequently infect humans
BABESIA SP
► There are >100 specicies of this intracellular
parasite.
► Babesia microti is the predominant human pathogen,
endemic to the Midwest.
► 10-20% of adults are seropositive in endemic areas
► Natural parasite reservoir is rodents
► Carried by the hard-bodied Ixodes Deer tick.
► Also carries agents for Lyme Disease, and
Ehrlichoisis.
► Can also be transferred transplacentally and through
blood transfusion.
Babesia in erythrocyts
Presence of 4 daughter merozoites in a tetrad .
Never seen in malaria.
Clinical presentation
► Ranges from asymptomatic infection to fatal
illness (rare)
► No direct correlation between parasitemia and
severity.
► More severe infection tends to occur in
immunnocompromised, elderly, and the very
young.
Clinical presentation
► The extreme end of the spectrum is often
described as a malaria-like infection;
symptoms may include malaise, chills,
mylagia, anemia, fatigue, and fever .
Some cases also described emesis,
night sweats, weight loss, and hematuria.
Life cycle
► The trophozoite is very similar to the ring form
of the Plasmodium species
► The organism (sporozoite) is transmitted by a
tick and enters the red cell where it undergoes
mitosis and the organisms (merozoite) are
released to infect other red cells. Ticks acquire
the organism during feeding on an infected
individual. In the tick, the organism divides
sexually in the gut and migrates into the salivary
gland
Special Case – Splenectomy
► Illness appears suddenly, with hemoglobinuria
as the presenting symptom followed by jaundice
due to severe hemolysis.
► Parasitemia can reach 80% of RBCs
► Can be a medical emergency.
► In the most severe cases, patients develop a
shock-like picture, with renal failure and
pulmonary edema.
► Chronic disease with many relapses over
months to years may occur if not treated.
Co-Infection
► It is estimated from serologic surveys that as many as
13% of Lyme disease patients in babesia-endemic areas
are coinfected with B. microti
► The initial symptoms of both babesiosis and Lyme
disease overlap significantly.
► Like babesiosis, Lyme disease also presents with
nonspecific symptoms of fever,fatigue, and other flu-like
symptoms.
► Patients coinfected with B. microti and B. burgdorferi
experience more severe symptoms, but does not
increase the duration of Babesia parisitemia.
► Doxycycline will not kill Babesia.
Diagnosis
► Diagnosis is based on clinical suspicion and
history of exposure.
► Thick and thin smears remain most clinically
used .
► Various PCR detection assays are available
for detection of B microtic and other species.
► Indirect fluorescent antibody test can also be
used as a confirmatory test.
► Can have false negatives (HIV) or false pos
(autoimmune)
Treatment
►
Current treatment is Quinine plus Clindamycin
► 72% receiving quinine and clindamycin had side effects
attributed to the drugs—diarrhea, tinnitus, or vertigo
► 15% receiving atovaquone plus azithromycin
experienced side effects (usually diarrhea or rash).
► For severe cases (asplenic) with high levels of
parasitemia, RBC exchange transfusions may also be
necessary.