Trypanosomiasis and Its Transmission

Trypanosomiasis Lecture Notes

• Trypanosomes were first described in frogs in 1855.
• Griffith Evans identified T. evansi as the agent of surra (a horse and camel disease) in 1880.
• David Bruce identified T. brucei as the cause of Nagana and demonstrated transmission by Tsetse flies.
• Trypanosomiasis, also known as sleeping sickness, is endemic to sub-Saharan Africa.
• Trypanosoma brucei is the causative agent, a type of extracellular flagellated protozoan parasite.
• Two morphologically similar subspecies cause human trypanosomiasis: T. brucei rhodesiense (East African or Rhodesian African trypanosomiasis) and T. brucei gambiense (West African or Gambian African trypanosomiasis).
• Transmission to humans occurs via the bite of infected Glossina (tsetse) flies.
• Glossina palpalis is the main vector in West and Central Africa, spreading 98% of reported sleeping sickness cases causing chronic infection.
• Glossina morsitans is the vector in East and Southern Africa, accounting for less than 2% of cases resulting in an acute infection.
• The main epidemiological factor in human African trypanosomiasis (HAT) is contact between humans and tsetse flies. Factors influencing the disease spread include tsetse fly density, changing feeding habits, and expanding human development into tsetse fly-infested areas

Morphology of Trypanosomes

• Trypomastigotes: Found in blood/lymph and tissue spaces of various organs, including the central nervous system. Characterized by spindle shape, central nucleus, and a free undulating membrane.
• Epimastigotes: Present in the salivary glands of the vector (tsetse fly) and culture media.
• Amastigotes: Intracellular stages.

Morphological Forms of Trypanosomes

• trypomastigotes - kinetoplast is anterior
• epimastigote - kinetoplast is central
• amastigote - kinetoplast is central. Amastigotes are intracellular circular with no flagellum

Life Cycle of Trypanosoma brucei gambiense and T. b. rhodesiense

• Infected tsetse fly injects the parasite (MT) into mammalian skin during a blood meal.
• Parasites enter lymphatic and blood systems, transforming into bloodstream trypomastigotes.
• Trypomastigotes circulate to other sites.
• In the fly's midgut, parasites turn into procyclic trypomastigotes, multiply via binary fission and then become epimastigotes.
• Epimastigotes migrate to the fly's salivary glands and develop into infective forms (MT).

Mechanism of Disease Transmission

• The primary method of transmission is through the bite of an infected tsetse fly.
• Other possible methods include mother-to-child transmission across the placenta, mechanical transmission by blood-sucking insects, accidental needle pricks in laboratories, and sexual contact.

Sleeping Sickness in Man

• Infection develops in two stages:
• First, a haemo-lymphatic stage, where the parasite initially multiplies in blood/lymph and various organs (mainly lymph nodes).
• This is followed by a meningoencephalic stage, characterized by severe neurological involvement and symptoms.

Clinical Picture of Haemo-Lymphatic Stage

• Incubation period: 2 weeks.
• Characteristic local inflammation (chancre) appears 5-15 days post-bite.
• Intermittent fever, general malaise, myalgia, arthralgia, and headache appear 3 weeks post-bite.
• Generalized or regional lymphadenopathy (with Winterbottom sign characteristic of gambiense).
• Facial edema, skin rashes, and anemia can occur.

Clinical Picture of Neurological/Meningo-encephalitic Stage

• Progression: 300-500 days for T.b. gambiense; 21-60 days for T.b. rhodesiense.
• Persistent headaches, loss of appetite/weight loss, and wasting syndrome.
• Daytime somnolence followed by nighttime insomnia, and neurological/mental symptoms.
• Progressive neurological involvement leading to dementia, behavioral changes, mood swings, depression, confusion, and sensory disturbances.
• Sleep cycle disruptions (sleeping sickness), coma, and eventually death.

Physical Findings

• Early/haemo-lymphatic stage: Indurated chancre at bite site, skin lesions (trypanids), and lymphadenopathy (axillary/inguinal or cervical, characteristic of gambiense).
• Late/neurologic stage: Kerandel sign (delayed pain on soft tissue compression), behavioral changes, seizures, stupor/coma and psychosis, sensory disorders.

3 Steps of Disease Management

• Screening: Serological tests (for T. b. gambiense) and examination for swollen cervical lymph nodes.
• Diagnosis: Assessing presence of the parasite in body fluids.
• Staging: Clinical evaluation and analysis of cerebrospinal fluid obtained by lumbar puncture to determine disease progression.

Diagnostic Considerations

• Hemolymphatic Stage: Differential diagnosis for recurrent fever includes malaria, HIV, borreliosis, brucellosis, typhoid, and other enteric fevers. Lymphadenopathy DDx includes TB, lymphadenitis, HIV infection, and cancer.
• Neurologic Stage: Differential diagnosis for mental status changes includes TB, meningitis, and HIV-related opportunistic infections (including cryptococcal meningitis).

General Blood Studies and Serology

• Blood tests may show anemia, hypergammaglobulinemia, low complements, elevated ESR, thrombocytopenia, and hypoalbuminemia.
• A standard assay called CATT (card agglutination test for trypanosomiasis) aids in West African trypanosomiasis diagnosis.
• Other tests include antigen detection assays (e.g., ELISA), various fluid/tissue cultures, antibody detection in CSF, intrathecal spaces, PCR tests, and serum proteomics.
• Isoenzyme and RFLP analysis help confirm the parasite subspecies.

Laboratory Diagnosis of Human African Trypanosomiasis

• Blood smears (wet or Giemsa-stained thick smears) to detect motile trypomastigotes.
• Hematocrit centrifugation technique or mAECT (miniature anion-exchange centrifugation technique).
• Chancre aspirate or lymph node/bone marrow aspirate as wet preparations.
• Examination of cerebrospinal fluid (CSF) for trypanosomes, WBC counts, protein levels, and IgM.
• Identify Mott cells (large eosinophilic plasma cells with IgM).

Diagnostic Imaging

• CT Scan and MRI for cerebral edema and white matter enhancement in late-stage trypanosomiasis.
• EEG analysis in neurologic involvement reveals slow-wave oscillations (delta waves).

Antigenic Variation in Trypanosomes

• Trypanosomes evade the immune system via antigenic variation of their surface glycoproteins (SVGs).
• Possessing about 1,000 variant forms of the surface antigen, a trypanosome can switch to a different variant, creating a new generation not targeted by immune factors from the previous generation.
• Increased total IgM level in serum is linked to antigenic variation.

Waves of Trypanosome Expansion

• Coat variation enables the parasite to evade immune responses.

Treatment of Human African Trypanosomiasis

• First Stage: Pentamidine (gambiense infection) or Suramin (rhodesiense infection).
• Second Stage: Melarsoprol (disadvantageous effects), Eflornithine (less toxic but complicated), or Nifurtimox-eflornithine (NECT).

Prevention and Control

• Avoid travel to heavily tsetse fly-infested areas.
• Inspect vehicles before entry in endemic regions.
• Wear long clothing in neutral colors.
• Treat asymptomatic carriers (via CATT/lymph node aspiration).
• Consult specialists for early and late-stage HAT.
• Conduct long-term monitoring after treatment (repeat blood smears, lumbar punctures).
• Utilize vector control strategies (multisectoral approach).

Tsetse Trap

• Tsetse fly traps use cow urine scent to lure flies.
• The trapping design—with black cloths in the middle—induces settling and kills flies.

American Trypanosomiasis (Chagas Disease)

• Causal agent: Trypanosoma cruzi.
• Leading cause of cardiac disease in Central/South America, spread via triatomine bug feces contact.
• Triatomine (kissing) bugs thrive in poor housing.

Morphology of Trypanosoma cruzi

• Trypomastigotes are slender, C or U-shaped with a centrally located nucleus and a large, bulging, peripheral kinetoplast.
• Amastigotes are obligate intracellular forms.
• Epimastigotes are spindle-shaped, have a kinetoplast anterior to the nucleus, and an undulating membrane.

Life Cycle of Trypanosoma cruzi

• Infected triatomine bug releases trypomastigotes in its feces near the bite site.
• Trypomastigotes enter the host via wounds/mucosa, invade cells, differentiate into amastigotes, and then trypomastigotes.
• Trypomastigotes infect various tissues and transform back into amastigotes and then bloodstreams.
• Ingested trypomastigotes develop into epimastigotes in the bug's midgut.
• Parasites multiply in the midgut and differentiate into infective metacyclic trypomastigotes in the hindgut.

Transmission of Chagas Disease

• Natural transmission: bite of an infected Triatominae (kissing) bug.
• Accidental ingestion: contaminated food/feces from an infected bug or marsupials.
• Congenital transmission: mother-to-child.
• Organ transplantation/blood/blood product transfusion from infected donors.
• Through infected mother's milk.
• Accidental laboratory infections.

Clinical Picture of Acute Chagas Disease

• Incubation: 7-14 days after bug bite.
• First symptom: bug bite.
• Chagoma: red nodule at the inoculation site.
• Romaña Sign: unilateral periorbital edema.
• Flu-like illness in some cases - (headache, chills, irritability, malaise, myalgia, lymphatic enlargement, and splenomegaly.

Clinical Picture of Chronic Chagas Disease

• Heart damage (congestive heart failure).
• Oesophageal megaesophagus leading to dysphagia.
• Colon megacolon and constipation.
• CNS or thyroid involvement.

Diagnosis of Chagas Disease

• Presumptive: Epidemiological history, bug bite, chagoma, Romaña's sign and chancre aspirate.
• Laboratory: CBC, elevated transaminase levels, lymph node, liver or spleen biopsy, Giemsa-stained smears, blood culture, xenodiagnosis, serological tests (CFT, IFAT, ELISA, PCR), and Cruzin test.
• Diagnostic Imaging: ECG, chest X-ray, cardiac, and colonic involvement MRI examinations,Barium enema

Treatment and Management of Chagas Disease

• Medical Care (Acute Stage): Nifurtimox or Benznidazole to target blood stream trypomastigotes. Supportive treatment for chronic Chagas disease (such as bed rest).
• Medical Care (Chronic): Patients with bradydysrhythmias/atrial fibrillation. Embolism/thrombosis management. Esophageal dysphagia may be treated with pneumatic dilation.
• Surgical Care (Chronic): Reserved for severe cases with persistent or severe damage, especially cases of dolichomegaesophagus (and other critical cases), Laparoscopic transhiatal subtotal esophagectomy, and sigmoid colon/rectum resection can be considered.
• Dietary measures: High-fiber diets and increased fluid intake in cases of colonic dysfunction.

Prevention and Control of Chagas Disease

• Environmental: Improve human dwellings to limit vector infestation.
• Personal: Personal hygiene (bed nets), food preparation/handling hygiene, separation of animal houses in infected areas, health education to changes behavior of high-risk populations.
• Control of Vectors: Insecticides, blood transfusions screening and testing of organs.
• Early Diagnosis: Test and treat patients with potential infection.
• Elimination of Reservoir Hosts: Focus on reduction of infected reservoir hosts (wildlife or domesticated animals).

WHO Response

• Global efforts to eliminate Chagas disease transmission, including epidemiological strengthening, diagnostic test development, and case management.

Recommended Books

• Clinical Parasitology, a handbook for medical practitioners by Harsha Sherry et al.
• Parasitology - Protozoology and Helminthology by K.D. Chatterjee.
• Medical Parasitology by Markell and Voge's.

Explore the world of trypanosomes and the diseases they cause, particularly focusing on sleeping sickness. This quiz covers the unique life cycle of Trypanosoma brucei and its transmission by the tsetse fly, including the various stages of infection. Test your knowledge on trypanosomiasis and its impact on sub-Saharan Africa.