PARASITOLOGY

MIDTERMS/LECTURE SECOND SEMESTER

THE HEMOFLAGELLATE

HEMOFLAGELLATES
● Trypanosoma cruzi
● Trypanosoma brucei gambiense
● Trypanosoma brucei rhodesiense Trypanosoma cruzi

★ Trypanosomiasis is a general term used to ● Etiologic agent of Chagas disease or American

refer to human diseases caused by Trypanosomiasis
● 1909 Carlos Chagas
hemoflagellates of the genus Trypanosoma.
○ Young medical student in Brazil
★ 1895- David Bruce
● The only trypanosome that has an intracellular
○ Scottish pathologist, identified Trypanosoma
amastigote stage
brucei
● Most heavily infected cell: myocytes and cells of the
○ causative agent of the trypanosomal
reticuloendothelial system
diseases known as NAGANA
● Intermediate host: Reduviid bugs
■ (a form of the disease often found
● Reservoir host: Zoonotic mammalian
in cattle) and sleeping sickness.
● Group Stercoraria
● ROMAÑA’S SIGN
★ The T. brucei first described has become known as
Trypanosoma brucei gambiense (often abbreviated as
T.b. gambiense). Trypanosoma brucei rhodesiense
MODE OF TRANSMISSION:
(T.b. rhodesiense) was not described until 1910 by
● Bite of Reduviid bug
Stephens and Fantham.
● Blood transfusion
● Transplacental route
★ Vectors of hemoflagellates found in PH
● Accidental ingestion of infected insect
○ T. cruzi: Triatoma and Rhodnius bugs

4 STAGES OF DEVELOPMENT MORPHOLOGICAL FEATURES:

● Amastigote
● Promastigote AMASTIGOTES
● Epimastigote ● Develops in cardiac muscles, brain tissue, visceral
● Trypomastigote tissue
● Round or ovoid in shape
1. Amastigote ● 1.5 to 4 um in diameter
● Oval-shaped ● Large red nucleus
● No protruding flagellum ● Has a dark-staining rod-shaped kinetoplast
2. Promastigote
● Nucleus: center
● Kinetoplast: anterior end PROMASTIGOTE
● Basal body: adjacent to the kinetoplast, anterior end ● Elongated spindle-shaped with pointed ends
● Short, free flagellum arises from the kinetoplast at the
anterior end
3. Epimastigote
● Nucleus: center
● Kinetoplast: anterior and immediately adjacent to EPIMASTIGOTE
nucleus ● Occur in the midgut in insect vector
● Basal body: adjacent to the kinetoplast, flagellum ● Elongated spindle-shaped with free flagellum from the
arises anterior continuing backwards along the margin of the
undulating membrane and ends at the kinetoplast
4. Trypomastigote which is situated anterior to the nucleus
● Nucleus: center
● Kinetoplast: posterior end
● Basal body: adjacent to the kinetoplast, flagellum TRYPOMASTIGOTES
arises ● Found in the peripheral blood in humans
● Long, slender forms: 16 to 20 um in length
● Short, stumpy forms: measure around 15 um
● Centrally located nucleus
● Corkscrew-like motility

RORRY 1
 ● In stained specimens, they are C-shaped; U- or
S-shaped

DIAGNOSIS
CLINICAL MANIFESTATIONS
● Specimens: Blood, Bone marrow aspirates, tissue
CHAGAS DISEASE biopsy
● Incubation Period: 1-2 weeks
● Divided into an acute and a chronic phase
ACUTE PHASE:
ACUTE STAGE
● Characterized by a focal or diffuse inflammation MICROSCOPY
mainly affecting the myocardium ● Thick and thin blood smear using GIEMSA stain
● Tissue biopsy
● Fever ● Concentration method: microhematocrit
● Chills
● Fatigue Xenodiagnosis
● Myalgia ● Trypomastigotes in endemic areas of South america
● Malaise ● Screening of blood bank donors

Attack of acute
● Recovery
● Transition to the chronic stage of disease CHRONIC PHASE:
● Death: usually occurs a few weeks after the attack ● ELISA
● Indirect hemagglutination
Signs and symptoms: ● PCR
● 8-12 weeks ● Indirect Immunofluorescence
● Severe acute disease
● <1% of patients Other tests:
● Acute myocarditis ● ECG
● Pericardial effusion ● Echocardiography
● Meningoencephalitis
● Oral transmission
● Chagoma
EPIDEMIOLOGY
○ Most common initial symptom is the
development of an erythematous nodule
○ Painful chagoma may last 2-3 months before WHERE:
subsiding ● South and Central and rarely in North America
● Brazil is the highest known prevalence of the
● T. cruzi through the ocular mucosa develop a diseases
characteristic conjunctivitis and unilateral edema
of the eyelids, a condition known as Romaña’s VECTORS:
sign. ● Kissing Bug
● Conenose Bug
● Triatomid Bug
CHRONIC PHASE
● Was initially thought to be autoimmune in nature RESERVOIR HOSTS
however was controversial ● Dogs
● Is manifested by fibrotic reactions that cause injury to ● Cats
the myocardium, cardiac conduction network, and
enteric nervous system PREVENTION AND CONTROL
● Chagas Cardiomyopathy ● Eradication of Reduviid Bug Nests
● Gastrointestinal Disease ● Construction of Homes without open design
● Congenital Chagas Disease ● DDT
● Educational Program
● Myocarditis
● enlargement of the colon (sometimes referred to
as megacolon) TREATMENT
● Esophagus (sometimes referred to as
megaesophagus), Recommended drugs
● Hepatosplenomegaly. ● Nifurtimox (Lampit)
● Cardiomegaly (enlargement of the heart) ● Benznidazole

Other Drugs

RORRY 2
 ● Allopurinol
● Itraconazole CLINICAL MANIFESTATIONS

● Human African trypanosomiasis

Antifungal agent
● Ketoconazole Two types:
1. Acute
New Drugs 2. Chronic
● Triazole derivatives
● Cruzipain Inhibitors ★ Sleeping sickness – manifests months or years
○ Undergoes two stages:
■ Early
■ Late
Trypanosoma rangeli
● CHANCRE (ULCER)
- Common associated disease and condition names: ○ First notable symptom that may appear is
NONE KNOWN the development of pain.
- Infections are generally asymptomatic and tend to ○ Surrounded by a white halo at the bitse site.
show no pathologic changes or signs of disease.
- Vector responsible for transmitting T. rangeli ● Lymphadenopathy
- Reduviid bug, (Rhodius prolixus- kissing ● Lymph node enlargement
bug) ● Apparent during this time

- Found in South and Central America particularly in ● Winterbottom’s sign

the areas of: ● Condition that refers to the enlargement of
- Brazil, Venezuela, Colombia, Panama, El the cervical lymph nodes in reference to this
Salvador, Costa Rica, Honduras, and trypanosomal disease.
Guatemala.
● Erythematous (red)
- Reservoir Host: Monkeys, Racoons, Dogs, Cats, ● Rash, pruritis,
Armadillos, and Rodents. ● Edema (swelling)

★ Generally thought to be a BENIGN INFECTION. ● Kerandel’s sign

● Delayed sensation to pain
EARLY PHASE
● Proliferate in the bloodstream and lymphatics
(hemolymphatic stage)
Trypanosoma brucei gambiense ● The early systemic phase lasts from 1 to 6 months

● Human African trypanosomiasis (HAT) a.k.a. “African LATE PHASE

sleeping sickness” ● Also known as “meningoencephalitic stage”
● West African sleeping sickness or Gambian ● Usually occurs 3 to 10 months
Trypanosomiasis
● Less than aggressive than East African Neurologic symptoms
counterpart ● Apathy
● Trypanosoma brucei gambiense is localized in ● Behavioral changes
western and central region of sub-Saharan Africa ● Headache
● Sleep pattern changes
➢ Trypanosoma brucei complex:
○ T.b. gambiense, ● Trypanosomes are able to evade the immune
○ T.b. rhodesiense, response of the host through a process called
○ T.b. brucei Antigenic variation

● Trypanosoma complex belongs to the trypanosome

family Salivaria Mode of Transmission
● M.O.T.: bite of blood-sucking Tsetse fly (Glossina ● Mother to child infection through placenta
spp.) ● Other blood sucking insects
● HAT is localized in remote regions of sub Saharan ● Accidental needle pricks
Africa
● Reservoir host: dogs, pigs, and sheep
● Chronic type (95% of HAT cases)
● WINTERBOTTOM’S SIGN DIAGNOSIS

● Specimen of choice
○ Blood

RORRY 3
 ○ Lymph node aspiration ● KERANDEL’S SIGN
○ CSF
● 2 primary species of tsetse fly vectors
● Thick and thin blood smears: fixed and stained by ○ Glossina morsitans
Giemsa ○ Glossina pallidipes
● Buffy coat concentration method: for detection of ■ Attacking animals may also transmit
parasites this organism
● Mini-anion exchange centrifugation technique Parasite biology
● Enzyme-linked immunosorbent assay ● Two types of African trypanosomiasis
● Immunofluorescence ● Trypanosoma brucei rhodesiense is clinically and
● Indirect hemagglutination test epidemiologically different from T. b. Gambiense
● Card agglutination test for trypanosomiasis (CATT) ● Reservoir host: domestic cattle
● Polymerase chain reaction ● Acute type (3% of HAT cases)
● Lumbar puncture: for CSF examination

EPIDEMIOLOGY CLINICAL MANIFESTATIONS

● Found in tropical West Africa and Central Africa ★ T. brucei rhodesiense sleeping sickness may appear
○ Especially in shaded areas along stream just weeks after infection
banks where the tsetse fly vector breeds
2 stages:
● 2 species of T.b. gambiense ● Early phase – hemolymphatic stage
○ Glossina palpalis ● Late phase – meningoencephalitic stage
○ Glossina tachinoides

Symptoms
● Fever
TREATMENT ● Myalgia
● Rigors
Early stage (Hemolymphatic stage) ● Rapid weight loss is common
● Suramin sodium ● Mental disturbance
○ Side effects: fever, rash, renal insufficiency, ● Lethargy
muscle pain, and paresthesia ● Anorexia may also be present

● Pentamidine ★ Winterbottom’s sign

○ Side effects: tachycardia, hypotension, and ○ May or may not be present
hypoglycemia
★ Lymphadenopathy is absent
Late stage (Meningoencephalitic stage)
● Melarsoprol
○ An arsenic-containing drug that can cause DIAGNOSIS
fatal arsenic encephalopathy but can be
prevented by coadministration of
corticosteroids ● Thick and thin blood films can be stained with Giemsa
○ Side effects: Jarisch-Herxheimer reaction ● Buffy coat concentration method
● Diagnostic techniques include: Enzyme linked
immunosorbent assay, indirect hemagglutination test,
2nd line drugs: mini-anion exchange centrifugation technique, and
● Nitrofurazone PCR
● Eflornithine
● Nifurtimox-Eflornithine combination treatment (NECT)

EPIDEMIOLOGY

Trypanosoma brucei rhodesiense

Reservoir host:
● Cattle and sheep
● Trypanosoma brucei rhodesiense also known as ● Wild animals
“East African Sleeping Sickness” Rhodesian
trypanosomiasis
● Found in Eastern and Central Africa
○ Esp. in brush areas
● Much more aggressive than T.b. gambiense
● Causes acute infection
● A vector-borne disease

RORRY 4