Protozoa 4a): African Trypanosomiasis Flashcards
What are the two forms of trypanosomiasis in Africa?
Trypanosoma brucei rhodesiense
- Southern and Eastern Africa
- Acute course of disease [weeks/months]
- This is responsible for <2% of sleeping sickness cases in Africa.
- Usually zoonotic – makes reservoir control more difficult
Trypanosoma brucei gambiense
- West and Central Africa
- Chronic course of disease [often over years]
- This is responsible for 98% of sleeping sickness cases in Africa
- Usually anthroponotic – makes reservoir control through screening easier
- Central African belt is conducive to Tetse survival which mean trypanosomiasis will be there
- Recent epidemics (all war regions):
- Southern Sudan
- Northwest Uganda
- Eastern Congo
- Northern Angola
- Tetse flies that live next to rivers (palpalis) transmit gambiense, while those on savanna land (morsitans) transmit rhodensiense (huge wildlife reservoir).
- This menas that there is currently an eradication program for gambiense running but due to the big wildlife reservoir of rhodensiense and eradication program is currently unfeasible
How is african trypanosomiasis spread?
Tsetse fly
Human African Trypanosomiasis is only found in Sub-Saharan Africa. 70% of cases nowadays are found in Congo. Uganda is the only country that has both types.
It is a vector-borne parasitic disease (like malaria).
The parasite responsible for the disease is Trypanosoma brucei.
The parasite is transmitted by the Tsetse Fly (genus: Glossina).
It can be transmitted mother to child during pregnancy, via blood transfusions/needle stick, WHO state that sexual transmission is documented.
It is known as sleeping sickness because of the prominent neurological features in the advanced stage of the disease.
What is the life cycle of African trypanosomiasis?
During a blood meal on the mammalian host, an infected tsetse fly (genus Glossina) injects metacyclic trypomastigotes into skin tissue. The parasites enter the lymphatic system and pass into the bloodstream . Inside the host, they transform into bloodstream trypomastigotes , are carried to other sites throughout the body, reach other body fluids (e.g., lymph, spinal fluid), and continue the replication by binary fission . The entire life cycle of African trypanosomes is represented by extracellular stages. The tsetse fly becomes infected with bloodstream trypomastigotes when taking a blood meal on an infected mammalian host , . In the fly’s midgut, the parasites transform into procyclic trypomastigotes, multiply by binary fission , leave the midgut, and transform into epimastigotes . The epimastigotes reach the fly’s salivary glands and continue multiplication by binary fission . The cycle in the fly takes approximately 3 weeks. Rarely, T. b. gambiense may be acquired congenitally if the mother is infected during pregnancy.
What is antigenic variation and what consequences does it have in african trypanosomiasis?
- Cyclical waving of trypanosome population in the bloodstream of a patient
- Due to antigenic variation
- This is more specific for gambiense and not so much for rhodensiense because it will just proliferate into very high numbers straight away, invade CNS and kill patients within weeks to months
What are the clinical features of african trypanosomiasis?
- Pathology is immune-mediated
- Local inflammatory reaction where bit is
- ‘chancre’ (like primary syphilis)
- Blood pathology
- Anaemia
- Enlargement of lymph nodes (Winterbottom’s sign -> palpable cervical lymph nodes)
- Early stage
- General symptoms
- Flu like
- Anaemia etc
- General symptoms
- Parasites cross blood brain barrier -> late stage
- CNS pathology
- Meningitis/encephalitis
- Behavioural abnormalities
- Disturbance of sleep patterns
- Patients don’t actually sleep more, just the pattern is completely random
- Coma as patients go into organ failure (many organs are affected, incl. the heart)
- Death
A trypanosomal chancre, where the subject has been bitten, usually occurs after a few days and takes about 3 weeks to disappear. In the early stages, waves of parasitaemia are associated with bouts of fever and a local adenitis in relation to the original bite is often found.
Some patients with parasitaemia are asymptomatic but most progress with episodes of fever, headache and arthralgia over the first few months.
Rhodesiense disease generally progresses more rapidly than the gambiense variety but both can end up after 2–4 years with CNS involvement and with the classical findings of hypersomnia, tremors, spasticity, convulsions and eventual coma. The hypersomnia often consists of excessive daytime sleepiness and restlessness, irritability and sleeplessness at night.
The prognosis is poor in those patients with CNS involvement. The diagnosis is definitively established by finding trypanosomes in the CSF. If MRI is available it can often indicate cerebral involvement.
What is the difference between active and passive surveillance in African trypanosomiasis?
How do we treat African trypanosomiasis stage 1 (haemoplymphatic)?
Due to toxicity of trypanocides, detection of parasite is essential before initiating treatment
- Tx has to happen under close medical supervision
- If severe cases, then treatment can be started prior to confirmation
- After tx, patients should be checked every 6 months over 24 months for relapse through clinical examination and lumbar puncture.
- Suramin used against T.b. rhodensiense disease in Eastern Africa. Give test dose as toxic.
How do we treat African trypanosomiasis stage 2 (meningoenecphalitic)?
Gambiense HAT
- Nifurtimox-eflornithine combination therapy (NECT)
- Nifurtimox PO for 10 days and eflornithine IV for 7 days
- In the event of a relapse after NECT or eflornithine: melarsoprol IV
- Prednisolone PO is frequently combined throughout the duration of treatment
Rhodensiense HAT
- Melarsoprol IV
- Prednisolone PO
What is a significant side-effect of melarsoprol?
Based on arsenic. Kill 5% of patients from reactive encephalopathy.
What drugs are currently in development against African trypanosomiasis?
Fexinidazole
A trial in Africa found fexinidazole to be 91% effective at treating sleeping sickness. Though less effective than nifurtimox with eflornithine in severe disease, fexinidazole has the benefit that it can be taken by mouth.
Fexinidazole is the first drug candidate for the treatment of advanced-stage sleeping sickness in thirty years.
How do we contain the spread of coronavirus?
- Vector control
- Insecticides: ground spraying/aerial spraying
- Trapping -> use small blue pieces of cloth that are attractive to the flies
- Target and insecticide
- Sterile insect treatment
- The island of Zanzibar was cleared of Tsetse flies by sterilising the male fly through irradiating them -> females only mate once so by using sterile males they were able to eradicate it
- Reservoir control
- Killing wildlife that acts as reservoir
What is the life cycle of trypanosoma?
Trypomastigotes are sucked up by both male and female tsetse flies during a blood meal so that both male and female tsetse flies are vectors of trypanosomiasis. Tsetse flies take a blood meal about every 2–3 days. Ingested trypomastigotes multiply in the stomach and reach the salivary glands in about 20 days.
During a blood meal on the mammalian host, an infected tsetse fly (genus Glossina) injects metacyclic trypomastigotes into skin tissue. The parasites enter the lymphatic system and pass into the bloodstream . Inside the host, they transform into bloodstream trypomastigotes , are carried to other sites throughout the body, reach other body fluids (e.g., lymph, spinal fluid), and continue the replication by binary fission . The entire life cycle of African trypanosomes is represented by extracellular stages. The tsetse fly becomes infected with bloodstream trypomastigotes when taking a blood meal on an infected mammalian host , . In the fly’s midgut, the parasites transform into procyclic trypomastigotes, multiply by binary fission , leave the midgut, and transform into epimastigotes . The epimastigotes reach the fly’s salivary glands and continue multiplication by binary fission . The cycle in the fly takes approximately 3 weeks. Rarely, T. b. gambiense may be acquired congenitally if the mother is infected during pregnancy.
Wha do trypanosomes look under the microscope?
MCQ tips and key words
Know the main countries affected by each type of trypanosomiasis
Learn the drugs ( & their side effects)
Examples of pyrethroids - Deltamethrin, Lambda-Cyhalothrin
