African Trypanosomiasis PDF

Alzaeim Alazhari University Faculty of Medicine Batch 25 Human African Trypanosomiasis (sleeping sickness) Presented by: Dr. Alaa Ali Mohamed Trypanosoma spp. among red blood cell Trypanosomiasis infection either caused by: 1- Trypanosoma brucei → african trypan...

Alzaeim Alazhari University Faculty of Medicine Batch 25 Human African Trypanosomiasis (sleeping sickness) Presented by: Dr. Alaa Ali Mohamed Trypanosoma spp. among red blood cell Trypanosomiasis infection either caused by: 1- Trypanosoma brucei → african trypanosomiasis (sleeping sickness). Or 2- Trypanosoma cruzi → chgagas disease.  Human African Trypanosomiasis (sleeping sickness) Caused by species of Trypanosoma brucei. 1- T. brucei gambiense: West and Central Africa trypanosomiasis, humans are the main reservoir of infection. 2- T. brucei rhodesiense: East and Southern Africa trypanosomiasis, Infected wild animals are the main reservoir of infection  Transmission is by the bite of tsetse flies (members of the genus Glossina) and the flies are only found in Africa. In general, the infected areas are found south of the Sahara and north of the Zambezi. Life Cycle: Tsetse flies ingest trypomastigotes during a blood meal from an infected mammalian host. In the midgut, parasites multiply by simple fission, penetrate the gut wall and migrate to the salivary glands. There the morphology changes, the kinetoplast coming to lie just in front of the nucleus, and the parasites are now called epimastigotes (crithidia), and continue to multiply.  The epimastigotes transform into the infective trypomastigote (the metacyclic trypanosome) which is found in the saliva about 20 days after the original infecting blood meal, and the fly remains infective throughout its normal lifespan of several months.  Pathogenesis: Local Effects: o At the site of the tsetse fly bite (Metacyclic trypanosomes injection). o An acute inflammatory lesion (trypanosomal chancre). o Multiplication of the parasite occurs in this lesion, resulting in inflammation, oedema, and local tissue destruction. o The parasites spread to the local lymph nodes and then disseminate in the bloodstream. o The trypanosomal chancre appears 3 or more days after the bite and typically increases in size for 2 or 3 weeks, and then it begins to regress. o The presence of a chancre is much more common in T. b. rhodesiense infection than in T. b. gambiense infection. Systemic Effects: Haemolymphatic Stage “ Stage 1”: o The multiplication of trypanosomes in the lymphatics leads to parasitaemia 5 -12 days after the bite. o There is widespread lymphadenopathy and histiocytic infiltration, followed by fibrosis. o The waves of parasitaemia are associated with fever. Systemic Effects: Meningo-encephalitic Stage “ Stage 2”: Parasites enter the central nervous system (CNS) via the choroid plexus or by transcytosis across endothelial cells.  T. b. gambiense T. b. rhodesiense Humans are the main A zoonotic infection, which is reservoir of infection, and so transmitted to humans better adapted and relatively accidentally causes well tolerated. pronounced systemic effects. The course of disease is sub The course of the illness cute or chronic. is relatively rapid. Parasitaemia may be Parasitaemia usually asymptomatic. causes severe incapacity. Immune Response and Pathogenesis: The main response to trypanosomal infection is antibody production, particularly IgM. Antibody production initially controls parasitaemia, but antigenic variation in parasite surface antigens means that immune control is incomplete and this leads to successive waves of parasitaemia, which may explain the fluctuating nature of the illness. Clinical Features: T. brucei gambiense: Stage 1: A trypanosomal chancre develops 1 - 2 weeks after the tsetse fly bite and resolves within several weeks. A small proportion of patients with parasitaemia are asymptomatic Fever, headache and joint pains are the main early symptoms, sometimes accompanied by fleeting areas of cutaneous oedema Posterior cervical lymphadenopathy (Winterbottom’s sign).  Moderate splenomegaly. Odd rounded skin rash, Generalized pruritus. Thickening of the facial tissues giving a sad or strangely expressionless appearance. NOTE: This stage usually lasts many months, sometimes even over 2 years. Occasionally, patients develop a rapidly progressive toxaemic disease which is fatal before the CNS is involved. However, most deaths occur after CNS invasion unless the patient develops an intercurrent infection. Stage 2: characterized by the insidious onset of neurological symptoms (headache, somnolence, listless gaze, extrapyramidal and cerebral signs as tremors, spasticity “mainly of the lower limbs” & ataxia) and CSF abnormalities. Behavioural changes, Psychiatric manifestations of agitation or delusions. Change the sleep pattern and as time goes by, sleeping periods become longer until the patient is sleeping most of the time, and may even fall asleep suddenly.  At this stage, speech and motor functions in general are usually severely disturbed. Convulsions are relatively uncommon. Kérandel’s sign “delayed hyperaesthesia” may occur. In advanced cases, the tendon reflexes are often exaggerated and the plantar responses may be extensor. Death usually occurs within a few months of CNS involvement becoming manifest, but may be delayed for up to a year. Clinical Features: T. brucei rhodesiense: The illness is more acute than the West African disease, with onset of symptoms a few days after the insect bite. Intermittent fever and rash are common features. Serous effusions, especially pleural and pericardial, are common and myocarditis occurs. lymphadenopathy is less prominent than in West African disease.  hepatocellular jaundice and anemia. Cardiac manifestations, such as arrhythmias and CCF, result in death prior to the onset of CNS disease. Untreated, this condition is fatal in weeks to months. Clinical features of CNS involvement are similar to T. b. gambiense, but death is more rapid and neurological features are more pronounced than behavioural changes. Diagnosis: Direct demonstration of parasite ✓ Blood film ▪ (wet prep and Giemsa stain) is more likely to be positive in the haemolymphatic stage and in East African trypanosomiasis (higher parasitaemia). ▪ Blood concentration techniques or buffy coat examination for scanty parasitaemia may increase sensitivity. Parasite of T.b. rhodesiense in the blood film. ✓ Aspirate from chancre or lymph node (acute infection only) (wet prep and Giemsa stain). ✓ Bone marrow biopsy useful in the early stages when other methods are negative. CSF examination ✓ Increased cell count (> 5/mm3), ↑ CSF pressure, and ↑ IgM and total protein concentrations. ✓ 5 -10 mL of centrifuged fluid should be examined as soon as possible for motile trypanosomes. ✓ Any patient with any CSF abnormalities should be regarded as having CNS disease. Serological: I. ↑ IgM II. The card agglutination test for trypanosomes (CATT) ▪ Simple to carry out, and gives good results in most areas of T. b. gambiense but is of no value in T. b. rhodesiense. ▪ It is a valuable test for screening populations as the results are obtained within 30 min. ▪ Disadvantages include limited sensitivity and specificity of the antigen, as trypanosomes share antigens with several other protozoa and bacteria. Treatment: depends on the infecting species, drug resistance patterns, and stage of disease. T.b. gambiense T.b. rhodisiense Stage Pentamidine OR Suramin 1 Suramin Stage Eflornithine OR Melarsoprol and 2 Melarsoprol and prednisolone* prednisolone* * steroid is to reduce risk of melarsoprol induced encephalopathy. Suramin: ✓ Administered intravenously. ✓Dose: a test dose of 5 mg/kg on day 1, then 20 mg/kg (max 1 g) should be given on days 3, 10, 17, 24 and 31. ✓Side effects: It is usually well tolerated, but fever, nausea and proteinuria may occur. Infrequent idiosyncratic anaphylactic reactions. Pentamidine: ✓ Administered intramuscularly or intravenously (IV administration avoids painful local tissue reactions ). ✓ Dose: 4 mg/kg/day for 7–10 days. ✓ Side effects: Syncope and hypotension. Hypoglycaemia may also occur. Melarsoprol: ✓ Administered intravenously. ✓ It is active against blood, tissue and CNS trypanosomes ✓ Melarsoprol therapy is normally preceded by 1-2 doses of suramin to clear blood, lymph and tissue trypanosomes. ✓ Dose: three or four series of three injections separated by 7 days at doses that range from 1.2 to 3.6 mg/kg. Recent studies suggest that shorter 10-day courses (2.2 mg/kg daily) may be as effective for T. b. gambiense. ✓Side effects: The major side-effect is a serious encephalopathy (reactive arsenical encephalopathy), occurs with a frequency of 2–10% and a case fatality rate of up to 50%. ** Prophylactic corticosteroids reduces the risk of an encephalopathy in T. b. gambiense. Peripheral neuropathy. Eflornithine: ✓Administered intravenously for the treatment of late stage T. b. gambiense infection. ✓Dose: 400 mg/kg/day in divided doses for 14 days. ✓It is relatively expensive and difficult to administer but less toxic than melarsoprol. ✓Side effects: gastrointestinal symptoms and anemia don't usually require treatment to be stopped. Monitoring cure: I. Patient symptoms should resolve after treatment. II. the CSF cell counts fall below 5/mL and for normal protein concentrations (may take 6 months or more). Failure of these parameters to become normal may be the first indication that treatment has been unsuccessful.  Full cure cannot be assumed unless a 2-year follow-up has been completed. If treatment of patients with CNS involvement has been delayed, a variable degree of neurological defect will persist (most commonly intellectual impairment). Relapse: In T. b. gambiense following treatment with suramin or pentamidine is often treated with melarsoprol; eflornithine can also be used. In T. b.rhodesiense is usually treated with a second course of melarsoprol. Prevention: ✓ Vector control. ✓ Surveillance with early treatment of identified cases (humans are only reservoir in T.b. gambiense). ✓ There is no vaccine.