American Trypanosomes (14-15) Flashcards
What is the prevalence of Trypanosoma cruzi Chagas disease?
8-10 million people infected in Latin America
Incidence of disease 500,000 new cases per year, 10,000 deaths per year
Highest burden of disability-adjusted life years (DALYs) lost among the NTDs (neglected tropical diseases)
Most important parasitic disease in Latin America
41% of 283 Andean mummies dates 9,000 years old positive for T. cruzi DNA
Humans are a very recent host - T. cruzi is >150 million years old
What is the T. cruzi vector?
Vectors: reduviid or Triatominae bugs (kissing bug)
Order Hemiptera, Family Reduviidae, Subfamily Triatominae
→ can take up lots of parasites
→ 8-10x body weight in blood
→ need to shed exoskeleton to grow (moult) - required a blood meal
What are the routes of transmission for T. cruzi?
Vector-borne by ‘kissing bug’ (80%)
Transfusion of infected blood (4-20%)
Congenital: mother to foetus (predominant form of transmission in US and Europe)
Accidental ingestion of infected sources (rare event)
What is the transmission cycle for T. cruzi?
- Triatomine (kissing) bug takes a blood meal → passes metacyclic trypomastigotes in fees, trypomastigotes enter bite wound or mucosal membranes such as the conjunctiva
- Metacyclic trypomastigotes penetrate various cells at bite wound site → inside cells they transform into amastigotes
- Amastigotes multiply by binary fission in cells or infected tissues
- Intracellular amastigotes transform into trypomastigotes then burst out of the cell and enter the bloodstream
→ trypomastigotes can infect other cells and transform into intracellular amastigotes in new infection sites, clinical manifestations can result from this infective cycle - Triatomine bug takes a blood meal → trypomastigotes ingested
- Epimastigote stage in midgut
- Multiplies in midgut
- Metacyclic trypamsatigotes in hindgut
- Triatomne bug takes a blood meal passing it to humans
(not saliva transmission (not efficient) - takes a blood meal, scratches site of bite, trypomastigotes in faeces enter)
What are the key triatomine species responsible for T. cruzi transmission?
~20 triatomic species responsible for T. cruzi transmission
key species: Rhodnius prolixus. Triatoma brasiliensis, Panstrongylus meglstus, Triatoma infestans, Triatoma dimidiata
→ T. Infestans highly domesticated vector in Southern Cone countries
What is the epidemiology of T. cruzi?
8 million people are infected
>10,000 deaths per year
Remains one of the biggest public health problems in 21 Latin American countries
In recent decades has spread beyond Latin America
Endemic to Latin America → reservoirs, vectors and contact between them - urbanisation
Non endemic regions → migration - risk for congenital transmission
USA: 300,000 infected persons live in USA, most of whom are migrants from Latin America
Enzootic T. cruzi transmission has been reported across the southern half of the US but locally acquired cases in humans are rare
What is the global distribution of T. cruzi?
Risk associated with migration
Chagas is long-lived infection with asymptomatic chronic carriers
Leads to unusual global distribution linked not only to transmission but migration
Subsequent (autochthonous) transmission is not vector-borne → rather mainly congenital, also blood transfusions and infected organ transplants
68,000-123,000 infected immigrants in Europe e.g. Bolivian’s make up 80% of immigrants in Spain
How did T. cruzi spread from wild animals to domestic animals and human beings?
T. cruzi was strictly a rural disease for decades but socio-economic changes, rural exodus, deforestation and urbanisation have transformed the epidemiological profile of the disease
→ led to expansion of endemic regions at the start of the 20th century - now large urban/peri-urban burdens
Triatomine bugs typically live in the wall or roof cracks of poorly constructed homes in rural or suburban areas - becoming active at night, biting exposed areas of skin, then defecating close to the bite
What are the epidemiological risk factors for T. cruzi?
Poverty / course construction → triatomic bugs favour habitats in poorly constructed houses
Deforestation and human colonisation of Triatomine habitats → provides abundant / stationary blood sources
Rural to urban migration → blood transfusions e.g. blood bank prevalence of 1.7% (Sao Paulo, Brazil) to 53% (santa Cruz, Bolivia)
Congenital transmission → e.g. 2-15% urban and 23-81% rural Bolivia
What is the time course from T. cruzi infection to chronic Chagas disease?
Infection
1-2 weeks → acute stage (asymptomatic/mild) - weeks/months
Chronic stage → life-long, asymptomatic Chagas disease (70-75% of infected subjects)
Latency of 10-20 years
Symptomatic Chagas disease (25-30% of infected individuals) → Chagas heart disease (85-95% of symptomatic subjects), chagas gastro-intestinal disease (5-10%), chugs heart/gastrointestinal disease
What occurs in the acute phase of Chagas disease?
Acute (symptomatic) form (4-8 weeks) - most often seen in children
→ fever, swelling lymph glands, liver and spleen enlargement, local inflammation of inoculation site (e.g. Romama’s sign)
→ abundant parasites in the blood stream (easy to diagnose)
→ mostly mild, self-limited symptoms e.g. fever that doesn’t come to medical attention
→ can be severe acute infection - myocarditis, meningoencephalitis - both life threatening
→ case fatality rate is estimated to be 0.25-0.5%
What occurs in chronic phase Chagas disease?
Chronic phase without treatment is life long
Cardiomyopathy (diseases of heart muscle) in 20-30% of chronically infected individuals
Develop digestive damage (megaviscera)
Peripheral nervous involvement
→ difficult to treat
How is Chagas disease diagnosed?
In the acute and early congenital phase → high parasitaemia - microscopy of stained blood smear - PCR or hemoculture
Chronic phase → parasitaemia levels drops, amastigotes remain in cardiac/skeletal muscle/macrophages, scarce trypomastigotes in blood
→ two serological IgG antibody tests due to low sensitivity
→ no satisfactory test to define parasitological cure (low PCR sensitivity)
→ no gold standard
What are the 2 effective drugs for treating Chagas disease?
Nifurtimox, Benznidazole
→ effective again acute and early chronicle phases only
→ serious / frequent side-effects (40%), more common with increasing age
In acute phase treatment reduces and shortens clinical severity and duration of detectable parasitemia - parasitological cure in 60-85% of patients treated in the acute phase
→ WHO recommends treatment for acute, congenital and reactivated T. cruzi infection, and for children (up to 18) with chronic infection
What are the drawbacks of the drugs for Chagas disease?
No drugs are effective for chronic phase
→ debate over usefulness in adults with long-standing infections - despite an impact on parasite serological parameters, a randomised trial of benznidazole did not significantly reduce levels of cardiac clinical deterioration over 5 year follow up
Clinical trials in progress for new drugs but hindered by no accepted reference assay to detect chronic T. cruzi infection (3x serological tests used) - PCR insensitive, antibody decay post cure is very slow
Drugs cannot be administered during pregnancy
Specific treatment to alleviate symptoms needed for cardiac, or digestive or neurological symptoms - but will not give parasitological cure
Serious side effects
Access: less than 1% of patients have access to Benznidazole
Only recommended in areas with vector control or non-endemic → due to re-infection and risks associated with treatment - governments dont mobilise benzidazol unless vector control implemented (re-infection makes it not cost effective)
Disease is poorly understood by health professionals in non-endemic areas → making detection difficult
Desperately need new drugs and to improve parasitological detection
What are some approaches to control of Chagas disease?
No vaccine
Endemic regions → sustained vector control of intra-domiciliary vectors in Latin America - prevent vector borne transmission
→ promote engagement with vector control activities
Endemic and non-endemic regions → screen blood transfusions and organ donation worldwide
→ screen pregnant women and children to control congenital transmission worldwide
→ promote health seeking behaviour and awareness among health professionals
What is the focus of control for Chagas disease?
Focus on prevention, interrupt transmission by:
→ controlling intra-domiciliary vectors in Latin America
→ screening blood banks for transfusions
→ screening organs for transplantation
→ screening for congenital infection (testing pregnant women)
This is because:
→ no vaccine
→ chemotherapy cannot be relied upon to prevent spread of infection - no solution to chronic infections (asymptomatic carriers), not widely available (expensive, distribution issues), vector infestation leads to high levels of re-infection
How is vector control used to control Chagas disease?
Indoor residual spraying → classic control - use of chemicals, important for delivery dose to be at correct level
→ contact insecticides - must lands on wall, must be inside
Insecticide impregnated nets (ITNs) (or curtains)
House improvement (environmental management) → plastering of walls - earth, cow dung, lime or cement mixes to seal gaps (vectors hide in the cracks)
Social interventions (education and community participation) → school teachers, community leaders, focus groups, meetings and house visits
→ sustainability is a key parameter in community participation
→ ‘good practices’ may be acquired, but abandoned if regarded low priority
Integrated Vector Management and political commitment → country wide approach
What is an example of successful vector control programme for Chagas disease?
Southern Cone Initiative → launched in 1991
→ Argentina, Bolivia, Brazil, Chile, Paraguay and Uruguay
→ domestic vector elimination
→ serological screening blood
→ housing improvement
→ international collaboration
Interruption of transmission achieved in… Uruguay - 1997, Chile - 1999, Brazil - 2002, Argentina - 2002, Bolivia - 2005, Paraguay - 2005
What is the domesticated vector for Chagas disease?
Triatoma infestans → highly domesticated - moved into houses
Where has seen re-emergence of Chagas disease?
Despite Southern Cone Initiative showing great success, Gran Chaco region has re-emergence
→ Argentina, Bolivia, Paraguay
→ 1.3 million km2
→ indigenous communities - marginalised communities often ignored by politicians
→ highest transmission
→ house infestation 82-100%
→ T. infestans infection with T. cruzi - 50%
→ typical living conditions - hot, dry, houses made out of framework of sticks and mud - cracks and spaces for vectors to hide
What rates of Chagas disease is present in Bolivian Chaco (Santa Cruz Department - largest of the 9 departments of Bolivia)?
→ house infestation index (proportion of houses infested): 18-73%
→ Triatomine infection prevalence with T. cruzi: 29-82%
→ house construction (wall crevices) main risk factor for persistent infestation
→ 20-30% infection prevalence in children <18yrs
→ 86-97% infection prevalence in adults >30yrs
→ 45% T. infestans populations variably resistant to IRS chemicals
Why is a higher prevalence of Chagas disease seen in pregnant women in rural community (Camiri) than less endemic state (Santa Cruz)?
Repeat vector infection exposure in Camiri sustains inflammatory responses at higher chronic levels, increasing cardiac morbidity, but possibly enabling exposed women to control parasitemia even in the face of pregnancy-induced Th2 polarisation
What is the method of surveillance for Chagas disease vectors?
Timed manual capture (TMC: 1 person looking for 30mins)
→ poor reproducibility
