African Trypanosomiasis

Slide 1 · African Trypanosomiasis

Transmission • antigenic variation • tissue pathology • CNS disease

Dr Abu Suraih Sakhri

MBBS, MD (Pathology)

www.abusuraihsakhri.com

Slide 2 · Learning outcomes

Distinguish the transmission ecology of gambiense and rhodesiense disease.

Trace VSG-mediated antigenic variation and explain recurrent fever.

Identify the tissue lesions of systemic and CNS disease.

Explain the diagnostic importance of cerebrospinal fluid examination.

Slide 3 · Core definition: Extracellular kinetoplastid disease

A blood- and tissue-associated infection that can evolve into sleeping sickness

African trypanosomes are kinetoplastid protozoan parasites.

They proliferate extracellularly in blood and tissue interstitial spaces.

Disease may progress from systemic inflammation to brain dysfunction.

Slide 4 · Kinetoplast: The defining cellular feature

The kinetoplast is a large DNA-containing structure within the parasite.

Kinetoplastid is a taxonomic descriptor, not a host-cell location.

Bloodstream African trypanosomes are described as slender forms figure caption.

Organism body

Kinetoplast = DNA-containing structure

Schematic — no diagnostic scale

Slide 5 · Where the organism lives

Bloodstream

Trypanosomes proliferate as extracellular organisms.

The circulating population encounters host antibodies.

Blood smears can reveal parasites.

Tissue interstitium

Parasites also inhabit extracellular tissue spaces.

A bite-site lesion can contain numerous organisms.

Tissue involvement produces inflammatory pathology.

Slide 6 · Clinical syndrome: The organ-system progression

Systemic illness

Sustained or intermittent fever

Lymphoreticular

Node and splenic enlargement

CNS progression

Brain dysfunction and wasting

The combination of fluctuating fever and later neurologic dysfunction is a diagnostic clue.

Slide 7 · Two human African trypanosome infections

T. B. Gambiense

Western and central Africa

Human-to-human transmission through tsetse bites

Active detection and treatment emphasized

T. B. Rhodesiense

Eastern and southern Africa

Transmission from infected animals through tsetse bites

Often acute and virulent; Vector reduction emphasized

Slide 8 · Reported disease burden: Historical textbook context

Gambiense infection

Approximately 800 cases reported in 2022.

Many were reported from the Democratic Republic of Congo.

Source describes a marked reduction over the preceding two decades.

Rhodesiense infection

Fewer than 50 cases reported in 2022.

Geographic focus is eastern and southern Africa.

Source emphasizes zoonotic transmission.

2022 textbook data only — not a present-day incidence comparison

Slide 9 · The tsetse fly connects reservoirs and recipients

Parasite source

Infected human or animal

Vector

Tsetse fly: Glossina

Recipient

Human bitten during blood meal

Reservoir differences change prevention strategy, even though the vector genus is the same.

Slide 10 · Development of African trypanosomes inside the fly

Fly stomach

Parasites multiply

Salivary glands

Further multiplication

Transmission form

Nondividing trypomastigotes

Next feeding

Parasites transmitted

Slide 11 · Transmission form: Nondividing trypomastigotes

The fly produces a nondividing trypomastigote stage before transmission.

This form enters another human or animal during the fly’s next blood meal.

Nondividing at transmission does not mean the infection remains nonproliferative in blood.

Life-cycle contrast

Nondividing transmission form → proliferating bloodstream forms

Slide 12 · From bite to systemic disease

Tsetse bite

Transmitted trypomastigotes

Extracellular growth

Blood and interstitial spaces

Host response

Inflammation and fluctuating fever

The parasite does not need an intracellular tissue phase to produce systemic disease.

Slide 13 · Why gambiense control emphasizes case finding

The described transmission chain includes an infected human source.

Undetected infections can remain part of that human-associated cycle.

The source therefore prioritizes active detection and treatment.

Control target

Find and treat human infection

Slide 14 · Why rhodesiense control emphasizes the vector

The infectious source may be a wild or domestic animal.

Human case treatment alone cannot directly eliminate animal-to-fly exposure.

The source explicitly prioritizes reducing infected vector populations.

Control target

Reduce infected tsetse flies

Slide 15 · Transmission interpretation: Choose the reservoir

Teaching vignette — hypothetical

An outbreak is reported in an area of eastern or southern Africa. Investigators identify tsetse exposure and infected local animals.

Which African trypanosome transmission pattern best fits?

Slide 16 · Transmission interpretation: Explanatory answer

Animal reservoir + eastern/southern Africa → rhodesiense pattern

The animal-associated pattern is characteristic of T. B. Rhodesiense.

Its geographic distribution aligns with eastern and southern Africa.

Vector reduction for this setting.

Slide 17 · Variant surface glycoprotein: The surface interface

Parasite coat

Abundant VSG on bloodstream forms

Host recognition

Anti-VSG antibodies generated

Population effect

Phagocyte-assisted elimination

The same antigenic coat that provokes host immunity becomes the target of immune evasion.

Slide 18 · A single abundant VSG dominates the coat

The surface is covered by variant surface glycoprotein (VSG).

The expressed surface protein is abundant and glycolipid anchored.

Antigenic identity of this coat determines antibody recognition.

Key property

A dominant surface antigen can be replaced by a different variant.

Slide 19 · How the host initially suppresses parasitemia

VSG recognized

Host makes specific antibodies

Effector collaboration

Antibodies with phagocytes

Majority killed

Parasite population contracts

Slide 20 · Partial clearance creates a population bottleneck

Immune control is substantial, but not sterilizing.

The anti-VSG response kills most circulating trypanosomes.

A small minority persists following antigenic change.

Those survivors can repopulate the bloodstream.

Slide 21 · Antigenic switching allows immune escape

Initial clone

VSG-A dominates

Genetic rearrangement

A few parasites display VSG-B

Immune escape

Anti–VSG-A misses switched clone

Expansion

VSG-B population increases

Escape depends on surface-antigen replacement, not disappearance of extracellular organisms.

Slide 22 · Successor clones explain relapse of parasitemia

A newly switched population proliferates after escaping the current antibody response.

The host subsequently develops antibodies against the new VSG.

Most of that successor clone is killed before another variant expands.

Selection principle

A changing surface antigen defeats a previously effective antibody response.

Slide 23 · Why waves of fever recur

Expansion

One VSG-bearing clone multiplies

Recognition

Host mounts anti-VSG response

Inflammatory peak

Fever accompanies clearance

Renewed expansion

Next VSG clone takes over

Slide 24 · The parasite carries a large VSG gene repertoire

Numerous distinct VSG genes exist in the parasite genome.

Only one VSG is expressed at a time by bloodstream parasites.

Sequential use of distinct genes supports recurrent antigenic change.

Genotype vs phenotype

Many VSG genes available; One VSG expressed on the surface.

Slide 25 · Gene distribution is not equivalent to gene expression

Genomic repertoire

VSG genes are distributed throughout the genome.

Different antigenic options exist in reserve.

Most are not simultaneously expressed.

Bloodstream transcription

Only VSG genes near chromosome ends are transcribed.

Expression is restricted to one bloodstream site.

One VSG dominates the current coat.

Slide 26 · Telomeric localization enables VSG expression

Scattered VSG genes

Genomic pool of alternatives

Chromosome-end site

Permissive transcription position

Active VSG

One surface variant produced

The expression site is a regulatory bottleneck between the gene repertoire and the antigenic coat.

Slide 27 · Homologous recombination renews the expressed VSG

Alternative VSG

Gene in genomic repertoire

DNA rearrangement

Mainly homologous recombination

Expression site

New VSG gene moved into active position

Surface change

Different VSG displayed

Slide 28 · One specialized RNA polymerase expression site

VSG gene transcription is linked to a specialized RNA polymerase.

That polymerase associates with only one bloodstream expression site.

This restriction limits expression to one VSG at a time.

Expression control

One active bloodstream expression site → one VSG coat

Slide 29 · Integrated mechanism of antigenic variation

Repertoire

Many VSG genes

Switch

Recombination into expression site

Single-gene output

One VSG coat expressed

Selection

Antibody escape and clone expansion

Slide 30 · What immune evasion does—and does not—require

Supported mechanism

Extracellular bloodstream growth

Host anti-VSG antibody responses

Sequential surface-antigen switching

Not required by this explanation

Intracellular sanctuary during blood stages

Simultaneous display of all VSG variants

Permanent failure to recognize any clone

Slide 31 · The inoculation site: Trypanosomal chancre

A large red, rubbery chancre can form at the bite site.

The lesion contains many parasites.

The local tissue reaction is predominantly mononuclear.

Skin surface with raised inflammatory lesion

Schematic; Not a clinical photograph

Slide 32 · Chancre pathology: Parasite meets inflammation

Bite site

Local parasite presence

Tissue response

Dense mononuclear infiltrate

Gross manifestation

Raised red, rubbery chancre

Slide 33 · From local chancre to chronic lymphoid changes

Early bite-site process

Localized chancre

Numerous parasites

Dense mononuclear inflammation

Chronic systemic process

Enlarged lymph nodes and spleen

Lymphocytes and plasma cells accumulate

Macrophages contain dead parasites

Slide 34 · Why lymph nodes become enlarged

Chronic disease produces lymphadenopathy.

Nodes are infiltrated by lymphocytes, plasma cells, and macrophages.

These accumulated cells contribute to increased nodal volume.

Histologic correlate

Lymphoplasmacytic–macrophage expansion

Slide 35 · Why the spleen becomes enlarged

Splenomegaly accompanies chronic infection.

The spleen is infiltrated by lymphocytes, plasma cells, and macrophages.

The tissue reaction reflects systemic persistence of the extracellular parasite.

Histologic correlate

Mononuclear inflammatory-cell infiltration of splenic tissue

Slide 36 · Macrophages may contain dead trypanosomes

Phagocytic debris ≠ intracellular parasite life cycle

The parasite remains extracellular while viable bloodstream forms circulate.

The source describes macrophages filled with dead parasites.

Finding dead parasites inside a phagocyte does not establish an intracellular replicative niche.

Slide 37 · Lymphocytes, plasma cells and macrophages

Lymphoid reaction

Lymphocytes infiltrate enlarged tissues.

Plasma cells are conspicuous in chronic lesions.

Plasma-cell immunoglobulin may accumulate as globules.

Phagocytic reaction

Macrophages accumulate in involved tissues.

Some contain dead parasites.

Their presence is consistent with immune clearance.

Slide 38 · Trypanosomes can concentrate in capillary loops

The source specifically notes capillary-loop concentrations.

Two named examples are the choroid plexus and renal glomeruli.

The observation concerns anatomic localization; No cause of this distribution is provided.

Anatomic sites

Choroid plexus • glomerular loops

Slide 39 · Entry into the CNS marks a major transition

Systemic infection

Extracellular blood and tissue parasites

Barrier breach

Parasites invade the CNS

Inflammation

Leptomeningitis develops

Progression

Encephalitic injury

Slide 40 · Leptomeningitis follows CNS invasion

CNS invasion is followed by inflammatory involvement of the leptomeninges.

Leptomeningitis is an anatomic-pathologic finding—not synonymous with a sleep symptom.

The disease can extend beyond the meningeal surface.

Leptomeningeal compartment

Underlying brain tissue

Schematic anatomy — not histology

Slide 41 · Inflammation extends along Virchow–Robin spaces

Leptomeningitis

Inflammation at meningeal surfaces

Perivascular route

Virchow–Robin spaces involved

Parenchymal disease

Wider CNS inflammatory injury

Slide 42 · Demyelinating panencephalitis is a late tissue lesion

The source identifies demyelinating panencephalitis after meningeal and perivascular involvement.

“Demyelinating” indicates injury to myelin; “panencephalitis” indicates diffuse encephalitic disease.

These pathologic findings help explain progressive neurologic dysfunction.

CNS pathology sequence

Leptomeningitis → perivascular extension → demyelinating panencephalitis

Slide 43 · Mott cells: Plasma cells with cytoplasmic globules

Mott cells are frequently identified in the source description.

They are plasma cells containing cytoplasmic globules.

The globules contain immunoglobulins.

Diagnostic vocabulary

Mott cell = immunoglobulin-globule–containing plasma cell

Slide 44 · Mott cells are host cells, not the parasites

Mott cell

A differentiated host plasma cell

Cytoplasmic immunoglobulin globules

Part of a chronic inflammatory reaction

Trypanosome

Extracellular kinetoplastid parasite

Variable VSG-bearing surface

Detected by visualization of organisms

Slide 45 · Progressive cachexia: The terminal systemic effect

Persistent disease

Repeated infection and inflammation

Clinical deterioration

Loss of energy and normal mentation

Progressive wasting

Severe cachexia

Slide 46 · Clinicopathologic map of organ findings

Site

Pathologic change

Clinical correlate

Bite site

Parasite-rich mononuclear chancre

Red, rubbery lesion

Nodes / spleen

Lymphoplasmacytic–macrophage infiltrates

Lymphadenopathy; splenomegaly

CNS

Leptomeningitis; demyelinating panencephalitis

Progressive brain dysfunction

Systemic

Persistent infection with progressive wasting

Cachexia; decreased energy

Slide 47 · Microscopy answers a different question from CSF staging

Diagnostic specimens

Blood smears

Lymph node material

Chancre material

Microscopy seeks visible organisms

CNS assessment

Cerebrospinal fluid examination

Determines whether CNS is involved

Findings direct the course of treatment

Slide 48 · Blood smears demonstrate circulating parasites

The organism is extracellular in blood.

Microscopic examination of a blood smear is a diagnostic method.

The textbook labels a figure of slender bloodstream trypanosomes, but the image was not supplied.

Evidence boundary

No authentic original smear image available in the supplied project files.

Slide 49 · Lymph node and chancre samples offer alternatives

Microscopic examination can be made on a lymph node or chancre specimen.

These sites align with tissue manifestations described in the morphology section.

The source does not provide sample-specific sensitivity or an exact diagnostic hierarchy.

Specimen principle

Sample an involved parasite-containing compartment.

Slide 50 · Why CSF examination changes management

Detecting trypanosomes ≠ determining CNS involvement

The bloodstream and peripheral tissues are not the whole clinical picture.

Central nervous system involvement determines treatment selection.

The source explicitly requires cerebrospinal fluid examination for this distinction.

Slide 51 · Source-based diagnostic reasoning pathway

Recognize syndrome

Fever ± node/spleen changes

Demonstrate parasite

Blood, node or chancre microscopy

Assess CNS

Cerebrospinal fluid examination

Plan treatment

Management depends on CNS status

Slide 52 · Case application: Febrile systemic illness

Teaching vignette — hypothetical

A patient with tsetse exposure has fluctuating fever, enlarged lymph nodes and an erythematous bite-site lesion. No CNS evaluation has yet been done.

What can peripheral microscopy establish, and what remains unknown?

Slide 53 · Case resolution: Organism detection is not staging

Confirm infection; Then assess CNS involvement.

Blood, lymph node or chancre microscopy can establish the presence of parasites.

Peripheral detection does not alone determine whether the CNS is involved.

The source requires examination of cerebrospinal fluid to guide treatment.

Slide 54 · Case application: Progressive brain dysfunction

Teaching vignette — hypothetical

A patient with established African trypanosomiasis develops deteriorating mentation after episodes of systemic illness. The clinician must determine whether the infection has entered the CNS.

Which pathology sequence is relevant, and what specimen is pivotal?

Slide 55 · Case resolution: Neuroinvasion changes the question

Neurologic dysfunction demands assessment of CNS disease.

CNS invasion produces leptomeningitis with perivascular extension.

Later disease may include demyelinating panencephalitis.

Cerebrospinal fluid examination is needed to determine CNS infection.

Slide 56 · High-yield distinction: Organism, host and lesion

Observation

Parasite-associated component

Host-associated response

Recurrent fever

Sequential VSG-expressing clones

Repeated anti-VSG responses

Chancre

Numerous extracellular parasites

Dense mononuclear infiltrate

Lymphoid enlargement

Dead organisms within macrophages

Lymphocytes, plasma cells, macrophages

CNS disease

Parasites cross BBB

Meningeal/perivascular inflammation; demyelination

Slide 57 · Five indispensable pathology associations

Glossina transmission; Gambiense human-associated and rhodesiense zoonotic patterns.

Extracellular bloodstream parasites with a single VSG coat.

Gene rearrangement enables sequential VSG variants and fever waves.

Chancre, lymphoid enlargement, Mott cells and progressive CNS injury.

Microscopic parasite detection must be complemented by CSF assessment.

Slide 58 · Recommended textbook reading

Robbins, Cotran & Kumar

Pathologic Basis of Disease, 11th edition (2026)

African Trypanosomiasis