Exercise 4: Blood and Tissue Flagellates: Leishmania and Trypanosoma

1. Trace the lifecycle of

a. Trypanosoma brucei gambiense and T.b. rhodisiense

b. Leishmania species

2. Discuss the pathogenesis, pathology, clinical manifestations and laboratory diagnosis of:
a. African Sleeping Sickness
*Pathogenesis, Pathology, Clinical Manifestations
Incubation Period (IP): 2-23 days
Trypomastigotes found in the bloodstream, LN, CNS (CSF) trypomastigote stage

 Lodge at site of injection or bite

Local inflammation
Into the bloodstream- parasitemia
LN: marked proliferation of endothelial cells in sinuses, leukocyte infiltration around the blood
vessels
CNS - arachnoid spaces - lymphoplasmacytic infiltrate - perivascular proliferation of endothelial
and neuroglia cells
Initial lesion: chancre - Elevated and painful - Later becomes indurated
During IP: nonspecific manifestations - Local irritation - Headache - Fever - Chills - Loss of
appetite
Symptomless patent period
Abortive, lymphatic stage, CNS type meningoencephalitis stage
Acute Febrile Period Hemolymphatic Stage
Invasion of LN
Fever
Enlargement of spleen, liver, LN
Winterbottoms sign enlargement of posterior cervical lymph nodes
Kerandels sign hyperesthesia; patient reacts in an exaggerated way to painful stimulus
Edema: hips, hands, legs
2nd stage: Meningoencephalitic Stage
CNS invasion Sleeping sickness stage
Headache
Mental dullness
Apathy
Muscle spasms
Disturbed
Death
From asthenia
Complications:
- Malaria
- Hookwork infection
- Schistosomiasis
- Pneumonia
- Dysentery
Laboratory Diagnosis
(+) symptoms
Endemic area
Demonstration of parasite in the blood, LN juice, sternal bone marrow, CSF
b. Chagas disease
Pathogenesis and Pathology
Organisms are engulfed by histiocytes in the adipose and muscle tissues and they multiply as
amastigotes.
At nearby LN, there is proliferation of histiocytes.
Chagoma appearance of small, painful, reddish nodule in the site of inoculation
Via blood or lymph: LN, lung, spleen, liver multiply in fixed histiocytes, muscle fibers,
Clinical Manifestations
IP: 7-14 d
Acute form

- Children: 20-30 d
- High fever, edema - LN, spleen, liver enlargement
Romaas sign edematous eyelid and conjunctiva; unilateral periorbital edema
Chronic form
- Digestive form: megaesophagus, megacolon (myenteric and mesenteric plexuses are destroyed)
- Cardiac enlargement due to direct destruction of heart muscle cells compensatory mechanism
- Neurologic form: aphasia, paraplegia, spastic paralysis
Laboratory Diagnosis
Demonstration of the parasite in the blood or tisues
Xenodiagnoses live human being; Laboratory-reared triatomine bugs are allowed to feed on
patients suspected of being infected then the bugs are later examined for the presence of T. cruzi.
Serologic test not so helpful in endemic area
c. Old World Cutaneous Leishmaniasis
Pathogenesis, Pathology
Early stage: proliferation of macrophages with amastigotes
Lymphoplasmacytic infiltrates
Epithelium: acanthosis (thickening of the epidermis), parakeratosis (nuclei are retained in the
superficial epidermis)
Necrosis, ulceration
Healing: granulation tissue (redness/bluish discoloration around lesion)
Secondary bacterial infection is common
Clinical Manifestations
IP: few days to 6 months
Single or multiple
Primary lesion: site of bite
Papules and nodules (solid raised lesion > 1 cm)
Ulcers
Relapsing lesions (leishmaniasis recidiva/lupoid leishmaniasis)
Laboratory Diagnosis: Amastigote
Puncture indurated edge of sore
Biopsy of lymphoid material at the edge of ulcer
Leishmanin reaction
o Montenegro skin test
o Intradermal injection of washed promastigotes
o Delayed hypersensitivity reaction
d. Mucocutaneous Leishmaniasis
Pathogenesis
Similar to oriental sore
Invade mucous membrane ( no keratinization)
Direct extension or metastasis (lymphatic channel or bloodstream)
Minimal to mutilation of the face
o Espundia- destruction of nose & palate
Pathology
Papules, ulcers: same as oriental sore
Espundia: nose, mouth, larynx
o Polyps in nasal cavity/pharynx
o Fungating & indurated ulcers
o Tongue, gums, buccal mucosa
o Histiocytes: containing amastigotes

Clinical Manifestations
Chiclero ulcer: face, ears
Pian bois (forest yaws): can metastasize
o Ulcerative lesion
Panamania: one or few ulcers, metastasis
Uta: self limiting, no metastasis (usually just one, from one sandfly)
Espundia: most notorious
o Mutilitation, persistence
DCL: papules to plaques to nodules
Laboratory Diagnosis
Puncture edge of initial ulcer
Nodules or ulcers at the mucus membrane
Culture- promastigotes
Montenegro test
(+) infected
(-) uninfected
e. Kala-azar or Visceral Leishmaniasis
Pathogenesis
Amastigotes multiply slowly
Macrophages free in bloodstream to viscera
Spleen, liver, bone marrow
Marked proliferation of macrophages
Leukopenia
Anemia
Thrombocytopenia
Spleen, liver enlarged
Lymphadenopathy
Hyperglobulinemia: relative increase in globulin levels because of hypoalbuminemia
Simulate as Aplastic Anemia
Pathology
Spleen: prominent Malphigian corpuscles (seen in the white pulp)
Liver: fatty infiltration, amastigotes
BM: parasites in macrophages
Heart: myocardial degeneration
Kidneys: hydropic change (swelling of renal tubular cells)
Lymph nodes: hyperplastic
Intestine: parasite in submucosa, ulcers
o Coinfection: amoebiasis, hookworm infections
PBS: anemia, leukopenia, low platelet count
Clinical Manifestation
IP 10 days to > 1 year (2-4 months)
Leishmanoma (nodular lesion at the site of bite): initial lesion
Malaise, headache, fever
Splenomegaly
Anemia
Emaciation
No ascites
Post kala-azar dermal leishmaniasis (PKDL): reactivation of the disease , localized to the skin
Laboratory Diagnosis
Splenic puncture

 BM biopsy
Lymph node aspiration
Montenegro skin test