Other Medically Important Protozoans

PARASITOLOGY LECTURE (FLORES)

Babesia spp.
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Apicomplexan
o Intracellular parasites
Blood parasite that cause malaria-like infections
Zoonotic infection; transmitted by ticks
Causitive agents
o Babesia microti
o Babesia divergens
Transovarian parasite can be transferred to the offspring
of the tick
o Usually seen in the life cycle of B. divergens
IS to tick: gametes
IS to man:
IS to mouse: sporozoite
DH: Tick (Ixodes)
IH:
o White footed mouse
o Deer
o Livestock
o Cattle
o Humans (accidental host)
MOT:
o Bite of an infected tick
o Blood transfusion
o Organ transplant
o Vertical transmission

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has been documented for "large" Babesia spp. but not for the
"small" babesiae, such as B. microti .

Humans enter the cycle when bitten by infected ticks. During a
blood meal, a Babesia-infected tick introduces sporozoites into the
human host . Sporozoites enter erythrocytes and undergo
asexual replication (budding) . Multiplication of the blood stage
parasites is responsible for the clinical manifestations of the
disease. Humans are, for all practical purposes, dead-end hosts and
there is probably little, if any, subsequent transmission that occurs
from ticks feeding on infected persons. However, human to human
transmission is well recognized to occur through blood
transfusions

Morphology
- Similar to malarial parasite
o No schizonts or gametocytes
- Up to 4 parasites per cell
- Incubation period: 1-12 months
- Gametocyte has no hemozoin pigment
- Merozoites:
o 4 in a cell
o Maltese cross appearance
- Immunocompetent humans: Asymptomatic

Life Cycle

The Babesia microti life cycle involves two hosts, which includes a
rodent, primarily the white-footed mouse, Peromyscus leucopus,
and a tick in the genus, Ixodes. During a blood meal, a Babesia-
infected tick introduces sporozoites into the mouse host .
Sporozoites enter erythrocytes and undergo asexual reproduction
(budding) . In the blood, some parasites differentiate into male
and female gametes although these cannot be distinguished at the
light microscope level . The definitive host is the tick. Once
ingested by an appropriate tick , gametes unite and undergo a
sporogonic cycle resulting in sporozoites
. Transovarial
transmission (also known as vertical, or hereditary, transmission)

Disease Manifestation and Pathogenesis
- Causes Babesiosis or Nantucket Fever or Redwater Fever,
Tick Fever, Texas Cattle Fever
- Most cases are asymptomatc and usually self-limiting
- Signs and symptoms:
o Mild chills and fever
o Hemolytic anemia
o Jaundice
o Hepatomegaly
o No malarial paroxysm

Risk Factors for Severe cases of Babesiosis
- Co-infection with Borrelia burgdorferi
o Transmitted with the same tick (vector)
o Causes Lyme disease
- Old age weak immune system

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Other Medically Important Protozoans

PARASITOLOGY LECTURE (FLORES)

Absence of spleen: Splenectomy (removal of the spleen,

which removes abnormal or distorted RBCs)
Immunodeficiency

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Diagnosis
- Examination of Giemsa stained smears
- Serology
o IFAT (Diagnostic titer = 1:64)
o Inoculation of Animals (Gold Hamster or gerbil)

Positive results: if hamster is

susceptible to the infection
- History of tick bite
- Molecular methods:
o PCR: more sensitive in detecting the parasite

Epidemiology
- Zoonotic
- Europe: Babesia divergens
- North America: Babesia microti
o North East, East Coast
o cases also reported in West Coast
- Human infections usually occur during spring and summer
- No human infections reported yet in the country

Treatment
- Clindamycin

Prevention
- Avoid tick bites
- Screen blood donors
- Apply insect repellants

Blood and Tissue Flagellates

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Hemoflagellates
Flagellates that are found in the blood and other fluids
(CSF) and in tissues
Vector borne parasites
Medically important genera
o Trypanosoma
o Leishmania

Generalities
- Only Trypanosoma and Leishmania infect humans
- Transmitted by a bite of an infected vector
- 4 morphological forms/stages
o Amastigote

No flagella

Found inside the cell; intracellular

Donovan-Leishman form

Nucleus

Kinetoplast: energy source; primarly

composed of DNA

Axoneme: root of flagellum

Basal body

Found intracellularly only

Promastigote

Leptomonas stage

First time to see flagella

Longer and slender

First stage to have flagella

Axoneme

Basal body

Kinetoplast: anterior to the nucleus

o Epimastigote

Crithidia

First stage to have undulating

membrane (1/2 body length)

Kinetoplast: Anterior to the nucleus

o Trypomastigote

Structures: Nucleus

Undulating membrane: full body

length

Kinetoplast: posterior to the nucleus

C-shape / S-shape / U-shape

All forms are found in Trypanosoma cruzi infections
Only the epimastigote and trypomastigote are seen in
Trypanosoma brucei
Leishmania infections: seen amastigote and promastigote
Diagnostic stages: amastigote and promastigote
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Trypanosoma cruzi
- Hemoflagellate
- Causes Chagas Disease or American Trypanosomiasis
- Final host: Human
- Diagnostic stage: trypomastigote found in blood
- Final host: humans
- Reservoir hosts:
o Armadillo
o Opossum
o Raccoon
o Dog
o Cat
- Intermediate host vector:
o Reduviid Bug (major)

Prefers lips during bug bite

o Triatomine bugs
o Kissing bug
- IS to humans: Metacyclic Trypomastigote

Life Cycle

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Other Medically Important Protozoans

PARASITOLOGY LECTURE (FLORES)

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An infected triatomine insect vector (or "kissing" bug) takes a blood

meal and releases trypomastigotes in its feces near the site of the
bite wound. Trypomastigotes enter the host through the wound or
through intact mucosal membranes, such as the conjunctiva .
Common triatomine vector species for trypanosomiasis belong to
the genera Triatoma, Rhodnius, andPanstrongylus. Inside the host,
the trypomastigotes invade cells near the site of inoculation, where
they differentiate into intracellular amastigotes . The amastigotes
multiply by binary fission and differentiate into trypomastigotes,
and then are released into the circulation as bloodstream
trypomastigotes . Trypomastigotes infect cells from a variety of
tissues and transform into intracellular amastigotes in new infection
sites. Clinical manifestations can result from this infective cycle. The
bloodstream trypomastigotes do not replicate (different from the
African trypanosomes). Replication resumes only when the
parasites enter another cell or are ingested by another vector. The
kissing bug becomes infected by feeding on human or animal
blood that contains circulating parasites
. The ingested
trypomastigotes transform into epimastigotes in the vectors
midgut
. The parasites multiply and differentiate in the
midgut
and differentiate into infective metacyclic
trypomastigotes in the hindgut .

Disease Manifestation and Pathogenesis
- Patients can be infected up to 20 years
- Chagoma: local inflammation; reddish nodule
o Found on site of bite / bite wound
- Romanas sign: early stages; type of periorbital swelling
(edema of eyelid and conjunctiva) (Eyelids: another site
that can be bitten)
- Acute phase
o Fever
o Lymphadenopathy (inflammation of lymph
nodes)
- Chronic phase
o No characteristic symptoms
- Manifestations of Chronic Phase
o Mega esophagus
o Mega colon
o Cardiomegaly

Cardiac arrhythmia / megacardium

Can lead to death

Pathogenesis
- Acute inflammatory reaction on bite
- Uses lectin like carbohydrates for binding
- Direct inflammatory response
o Chaga toxin
o Damage to infected cells
o Destruction of autonomic nerve ganglions
- Target cells:
o Cells of RES
o Cardiac cells
o Skeletal cells
o Smooth muscles

o Neuroglia cells

Diagnosis
- Cardiac symptoms are present if living in endemic regions
- Usually in South America (Brazil)
- Demonstration of trypanosomes in blood, CSF, tissues,
lymph (staining using Giemsa)
- Xenodiagnosis: to confirm, get a laboratory reared
reduviid bug; bite infected patient look for parasite
stages in the bug after
- Culture:
o Changs
o NNN
- Serology:
o IFAT
o Complement fixation
o ELISA

Epidemiology
- Occurs only in American continent
o Highest prevalence in Brazil
o More common in rural areas
o Chronic disease is more common
o Common in unsanitary housing conditions
o More fatal in young children
o Zoonotic
- Vector is found in Philippines but no reported cases

Treatment
- Nifurtimox
- Benznidazole

Prevention and Control
- Vector control
- Screening of blood
- Health education

Trypanosoma brucei complex
- 2 subspecies
o Trypanosoma brucei rhodesiense
o Trypanosoma brucei gambiense
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Other Medically Important Protozoans

PARASITOLOGY LECTURE (FLORES)

Etiologic agents of African sleeping sickness

Trypanosoma brucei rhodesiense
a. Causes Rhodesian or East African Sleeping
Sickness
b. Endemic East and South Africa
2. Trypanosoma brucei gambiense
a. Causes Gambian or
- Under microscope, same morphology
- To differentiate:
- Vector Transmitted Parasitic Infections
o Vector: Tsetse Fly (Glossina spp.)

T. b. r. G. pallidipes, G. morsitans
Life Cycle

2.

During a blood meal on the mammalian host, an infected tsetse fly
(genus Glossina) injects metacyclic trypomastigotes into skin tissue.
The parasites enter the lymphatic system and pass into the
bloodstream . Inside the host, they transform into bloodstream
trypomastigotes , are carried to other sites throughout the body,
reach other blood fluids (e.g., lymph, spinal fluid), and continue the
replication by binary fission . The entire life cycle of African
Trypanosomes is represented by extracellular stages. The tsetse fly
becomes infected with bloodstream trypomastigotes when taking a
blood meal on an infected mammalian host ( , ). In the flys
midgut, the parasites transform into procyclic trypomastigotes,
multiply by binary fission , leave the midgut, and transform into
epimastigotes . The epimastigotes reach the flys salivary glands
and continue multiplication by binary fission . The cycle in the fly
takes approximately 3 weeks. Humans are the main reservoir host
for Trypanosoma brucei gambiense, but this species can also be
found in animals. Wild game animals are the main reservoir host
of T. b. rhodesiense.

Morphology
- Epimastigote found in insect
- Trypomastigote found in mammalian host

Disease Manifestation
1. Trypanosoma brucei gambiense

Causes Gambian or West African Sleeping

Sickness
o Earliest sign: Trypanosomal Chancre

Patients will appear healthy

Blood smear: negative in early stages,

+ trypomastigotes

Patients experience fever once the

lymph nodes are affected.

Other manifestations include malaise,

weakness, night sweats, dizziness and
nausea
o Winterbottoms sign
o Chronic disease

CNS invasion

Sleeping sickness stage initiated

Severe headache

Increasing mental deterioration

Apathy

Meningoencephalitis

Manifestation of Kerandels Sign:

delayed sensation to pain
o Terminal Phase

Coma leading to death

Trypanosoma brucei rhodesiense
o Causes Rhodesian and East African Sleeping
Sickness
o Similar to Gambian Sleeping Sickness

But acute and rapidly progressing

CNS stgae takes place in the early

stages

Glomerulonephritis may also be seen

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Pathogenesis
- Generalized Lymphoid Hyperplasia
- Anemia
- Thrombocytopenia
- Hypergammaglobulinemia
- Immune evasion though: Variant Surface Glycoproteins
- Acute infection seen in Rhodesian Sleeping Sickness
- Chronic Infection seen in Gambian Sleeping Sickness

Diagnosis
- Physical findings and patient history
- Demonstration of trypomastogotes in:
o Blood
o CSF
o Lymph node aspirate
- Concentration of buffy coat
o Giemsa stain
- Serology
o IHAT
o ELISA
o Rapid tests
- Molecular methods
- Animal inculation and culture

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Other Medically Important Protozoans

PARASITOLOGY LECTURE (FLORES)

Epidemiology
- Vectors inhabit areas near river banks and streams
- Congenital transmission is possible
- Low prevalence rate (<1%)

Treatment
- Better prognosis if treatment started before CNS stage
- Pentamidine and Suramine (blood and lymphatic stage)
- Melarsoprol (late stage)

Leishmania spp.
- Vector Borne Parasitic Disese
- Vector: sandflies (Phlebotomus spp.)
- Obligate intracellular parasites
- Primarily a zoonotic disease
- Humans are infected by bite of sandflies
o Other MOT

Blood tranfusion

Contact

Contamination of bite wound

- Target cells: RE cells (Reticulo endothelial cells
macrophage)
- Leishmania tropica
- Leishmania braziliensis
- Leishmania donovani
- IS to man: promastigote
- IS to fly: amastigote

Life cycle

Leishmaniasis is transmitted by the bite of infected female

phlebotomine sandflies. The sandflies inject the infective stage (i.e.,
promastigotes) from their proboscis during blood meals
.
Promastigotes that reach the puncture wound are phagocytized by

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macrophages and other types of mononuclear phagocytic cells.

Progmastigotes transform in these cells into the tissue stage of the
parasite (i.e., amastigotes) , which multiply by simple division and
proceed to infect other mononuclear phagocytic cells . Parasite,
host, and other factors affect whether the infection becomes
symptomatic and whether cutaneous or visceral leishmaniasis
results. Sandflies become infected by ingesting infected cells during
blood meals ( , ). In sandflies, amastigotes transform into
promastigotes, develop in the gut (in the hindgut for leishmanial
organisms in the Viannia subgenus; in the midgut for organisms in
the Leishmania subgenus), and migrate to the proboscis .

Morphology
- Amastigote form is seen in mammalian host
o Purple dots = amastigote
- Promastigote form is seen in sand fly


Disease Manifestations
1. Cutaneous Leishmaniasis
- Other names:
o Old World Leishmaniasis
o Aleppo Button
o Delhi Boil
o Baghdad Boil
o Jericho Boil
- Etiology: Leishmania tropica
- Incubation period: weeks to months
- Elevated skin ulcers (painless)
o leaves an ugly scar
o highly disfiguring
2. Mucocutaneous Leishmaniasis
- Other names:
o American Leishmaniasis
o New World Leishmaniasis
- Etiologic agent: Leishmania braziliensis
- Incubation: weeks to months
- Disease Manifestations
o Initial stage: ulcers similar to Old World
Leishmania
o Later stage: spread to oronasal and pharygneal
mucosa

Espundia

Tapir nose

Chiclero ulcer
3. Visceral leishmaniasis
- Other names:
o Kala-azar
o Dumdum fever
o Black fever
- Etiology: Leishmania donovani
- Incubation perios: 1-3 months
- Manifestation

o Dromedary fever: fever with twice daily
elevations
o Splenomegaly
o Cachexia
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Other Medically Important Protozoans

PARASITOLOGY LECTURE (FLORES)

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Hepatomegaly
Darkening of skin (forehead, temples, around
the mouth)
Dermal leishmanoid lesions may be rarely
seen

Epidemiology
- Endemic in 88 countries on 5 continents
- Endemic areas:
o Visceral Leishmaniasis: Bangladesh, Brazil, India,
Nepal, Sudan
o Cutaneous Leishmaniasis: Afganistan, Brazil,
Iran, Peru, Saudi Arabia, Syria
o Mucotaneous Leishmaniasis: Brazil, Eastern
Peru, Bolivia, Paraguay, Ecuador, Colombia,
Venezuela

Diagnosis
- Demonstration of Lesions
- Tissue Biopsies
- Skin Biopsies
- Examination of BM, spleen, lymph node
- Montenegro skin test Leishmanin Skin Test
- Serology: IFAT
- Culture: NNN
- Molecular methods

Treatment
- Antimony Compounds
o Soidum Stibogluconate
o n-methyl-glucamine antimonate