Sleeping sickness diseases (Trypanosoma spp.)

📚 AFRICAN TRYPANOSOMIASIS (SLEEPING SICKNESS)

🖇 I. INTRODUCTION TO BLOOD FLAGELLATES

📌 Lecture Focus

• Parasites affecting Central Nervous System (CNS)
• Can cause cystic lesions or other CNS lesions

📌 Classification

• Trypanosoma = blood flagellate

🚨 Definition: Blood Flagellates

• Protozoa that swim in the blood
• Use flagellum for movement

🚨 Flagellum Terminology (Exam Point)

• Flagellum also called mastigote

📌 Behavior

• Swim in blood
• Subsequently invade tissues

🖇 II. MORPHOLOGY OF TRYPANOSOMA (FOUR FORMS)

📌 General Note

• Parasite takes 4 different forms (shapes) in blood or tissue
• Term mastigote = flagella
• Adding letter 'A' (Amastigote) = NO flagella

🟠 THE FOUR FORMS:

🟣 1. AMASTIGOTE

• Shape: Round or oval
• Nucleus: Eccentric
• Kinetoplast: Present
• Flagellum: ABSENT (lacks flagellum)

🟣 2. PROMASTIGOTE

• Shape: Elongated
• Nucleus: Central
• Kinetoplast location: Posterior end
• Flagellum: Free flagellum exits from kinetoplast

🟣 3. EPIMASTIGOTE

• Shape: Elongated
• Nucleus: Central
• Kinetoplast location: Near nucleus
• Special feature: Exiting flagellum interacts with parasite's wall
• • Forms undulating membrane
• Possesses: Free flagellum + undulating membrane

🟣 4. TRYPOMASTIGOTE

• Shape: Elongated
• Nucleus: Central
• Kinetoplast location: Anterior end
• Features: Undulating membrane + free flagellum

🖇 III. TRYPANOSOMIASIS CLASSIFICATION

📌 Disease Name

• Disease caused by Trypanosoma = Trypanosomiasis

📌 Classification Types

• African type
• American type

📌 American Type (Brief Note)

• Causes Chagas disease
• Transmitted by Triatomine bug (kissing bug)
• NOT focus of this lecture

🚨 Lecture Focus: (Exam Point)

• African Trypanosomiasis
• Causes Sleeping Sickness

🟠 A. SPECIES & VECTORS OF AFRICAN TRYPANOSOMIASIS

🚨 Vector: (Exam Point)

• Tsetse fly (Glossina)

📌 Two Species (by Geographic Location):

WEST AFRICAN TYPE:

• Species: Trypanosoma brucei gambiense
• Vector: Glossina palpalis (Tsetse fly)

EAST AFRICAN TYPE:

• Species: Trypanosoma brucei rhodesiense
• Vector: Glossina morsitans (Tsetse fly)

🟠 B. DIFFERENCES: WEST vs EAST AFRICAN SPECIES

🟣 WEST AFRICAN (gambiense):

📌 Trypomastigote in Blood:

• Less plentiful (lower count)

📌 Culture in Lab Animals:

• Does NOT grow
• Cannot be cultured in lab animals

📌 Nuclear Shift:

• N/A

📌 Reservoir Host:

• Domestic animals (dogs, cattle, pigs)

📌 Clinical Course:

• Slower progression

🟣 EAST AFRICAN (rhodesiense):

📌 Trypomastigote in Blood:

• More plentiful (higher count)

📌 Culture in Lab Animals:

• CAN be cultured in lab animals

📌 Nuclear Shift (Post-Culture):

• Nucleus shifts posteriorly
• (Posterior nuclear shift)

📌 Reservoir Host:

• Wild game animals

🚨 Clinical Course: (Exam Point)

• More rapid and fatal course
• More virulent

🖇 IV. LIFE CYCLE & MECHANISM OF DISEASE

📌 Transmission Method

• Disease transmitted by arthropod vector

🟠 STEP-BY-STEP LIFE CYCLE:

🟣 1. INFECTION OF VECTOR (TSETSE FLY):

Step 1: Fly bites infected host

Step 2: Ingests Trypomastigote

📌 Trypomastigote Characteristic:

• Polymorphic = multiple shapes
• Has short, medium, long sizes

Step 3: Inside fly's intestine

• Trypomastigote transforms into Epimastigote

Step 4: Epimastigote migration

• Migrates through fly's digestive system
• Reaches salivary gland

Step 5: In salivary gland

• Transforms into Infective Stage

🟣 2. INFECTIVE STAGE (Exam Point)

🚨 The infective stage is:

• Short, stumpy, metacyclic Trypomastigote

📌 Timeline:

• Entire transformation process takes weeks

🟣 3. TRANSMISSION TYPE (Exam Point)

🚨 Transmission is BIOLOGICAL

• Parasite undergoes morphological changes (life stages) inside vector's body
• NOT mechanical transmission

🟣 4. INFECTION OF HOST (HUMAN):

• Infected fly bites non-infected person
• Transmits disease

🖇 V. CLINICAL MANIFESTATIONS & DISEASE PROGRESSION

📌 Incubation Period

• Approximately 2 weeks after bite

🟠 STAGES OF DISEASE PROGRESSION:

🟣 1. INITIAL STAGE (BITE SITE)

📌 Presentation:

• When fly first bites patient
• Nodule forms at site
• Called: Trypanosomal Chancre

🟣 2. LYMPHATIC INVASION (HEMOLYMPHATIC STAGE)

📌 Mechanism:

• Parasite travels via lymphatics
• Reaches lymph nodes

📌 Primary Location:

• Primarily infects posterior cervical region lymph nodes

🚨 Clinical Sign: (Exam Point)

• Enlargement of posterior cervical lymph nodes
• Called: Winterbottom's Sign

🟣 3. BLOOD STREAM INVASION

📌 After lymphatic stage:

• Parasite enters bloodstream

📌 General Manifestations:

• Fever
• Headache
• Muscle pain
• Joint pain
• Rash (erythematous rash)

📌 Bone Marrow Invasion:

• Leads to hypoplastic anemia

📌 Organ Effects:

• Enlarged liver and spleen (hepatosplenomegaly)

🟣 4. CNS INVASION (Most Dangerous Stage)

🚨 Significance:

• Final and most critical stage
• Invasion of Central Nervous System (CNS) - specifically brain

📌 Symptoms (Progressive):

• Severe headache
• Apathy (lack of concern)
• Slurred speech (like drunk person)
• Deep sleep
• Coma
• Death

🖇 VI. DIAGNOSIS

📌 Diagnostic Approach

• Clinical history
• Physical examination
• Laboratory testing

🟠 DIAGNOSTIC METHODS:

🟣 1. CLINICAL HISTORY

• Confirm presence of insect vector in area

🟣 2. CLINICAL PICTURE

• Observe chancre, OR
• Observe Winterbottom's Sign

🟣 3. LABORATORY SAMPLES

• Samples collected from:
• • Chancre
  • Lymph nodes
  • Blood
  • Cerebrospinal Fluid (CSF)

🟣 4. DIAGNOSTIC STAGE (Exam Point)

• Finding Trypomastigote in blood

🟣 5. CULTURE

• Only East African species (rhodesiense) can be cultured
• Culture in lab animals
• Undergoes posterior nuclear shift

🟣 6. SEROLOGICAL TEST

• Detection of IgM
• Detection of antigen/antibody

🖇 VII. IMMUNE EVASION MECHANISM

📌 Capability

• Trypanosoma capable of evading immune system

🚨 Genetic Diversity: (Exam Point)

• Genes of Trypanosoma brucei code for approximately 1000 different forms

📌 Mechanism

• Parasite changes its surface glycoprotein (glycoprotein coat)
• Prevents host's immune system from recognizing it

📌 Consequence

• Developing effective immunity is difficult
• Developing preventative measures is difficult

🖇 VIII. TREATMENT & CONTROL

🟠 A. TREATMENT

🟣 EARLY STAGE (Before CNS Involvement/Coma)

• Pentamidine, OR
• Suramin

🟣 LATE STAGE (Advanced Disease/Coma)

• Tryparsamide

🟣 USED IN BOTH EARLY & LATE STAGES

• Eflornithine

🟠 B. CONTROL

📌 Control Measures:

1. Control the vector (Tsetse fly)
2. Prophylactic drugs:
3. • Use Pentamidine
   • If traveling to endemic area

🖇 IX. SUMMARY OF KEY SIGNS (EXAM REVIEW)

🚨 Winterbottom's Sign: (Exam Point)

• Can be seen in African Trypanosomiasis
• Refers to swollen lymph nodes in posterior cervical region

🚨 Infective Stage: (Exam Point)

• Short, stumpy, metacyclic trypomastigote

Key Focus Areas for Exams:

• Four forms of Trypanosoma (Amastigote = no flagella)
• Mastigote = flagellum
• African Sleeping Sickness: West (gambiense) vs East (rhodesiense)
• East African more virulent, rapid, fatal course
• Vector: Tsetse fly (Glossina)
• Infective stage: short, stumpy, metacyclic trypomastigote
• Biological transmission (not mechanical)
• Winterbottom's Sign = posterior cervical lymph node enlargement
• Diagnostic stage: Trypomastigote in blood
• 1000 different genetic forms for immune evasion
• Treatment: Early (Pentamidine/Suramin), Late (Tryparsamide), Both (Eflornithine)