Leishmaniosis Flashcards
What is the vector of Leishmania and what genera are present in the old and new world?
Sandflies
Old World = Phlebotomus
New World = Lutzomyia
What is meant by “digenetic” life cycle?
Two stages - extracellular phase in the sandfly gut and intracellular phase in the mammalian host.
Describe the lifecycle of Leishmania
Promastigote enters the skin and then bloodstream via a sandfly bite. It enters macrophages where it becomes an amastigote. Following this amastigotes can burst out of the macrophage and infect other macrophages or disseminate to internal organs. Amastigotes can also be taken up by a sandfly.
What other routes of transmission are there? (include those which have been proven and those which haven’t been proven)
PROVEN Veneral Vertical Blood products/transmission Syringe usage
UNPROVEN
Direct contact
Ticks and fleas
In what tissues does the parasite replicate?
Macrophages
What is the outcome of disease determined by?
This is regulated by the host immunoinflammatory response.
How is the parasite killed?
TH1 biased immune response allowing production of iNOS and therefore NO for intracellular killing of the amastigotes.
A TH2 response may modulate inflammatory pathology but leaves the host more prone to infection from Leishmania
How can Leishmania evade the immune response?
Decrease Ag presentation
Reduce production of inflammatory cytokines
Increase production of immunosuppressive cytokines.
What needs to be taken into account when translating mice models to othermammals disease?
Mice have a very clear distinction between TH1 and TH2 responsed whereas other animals dont.
What are the types of severity in human infections and what factors contribute to the type that manifests?
Subclinical
Self-limiting disease
Non self-limiting (severe) disease
Factors:
Parasite diversity - infectivity, pathogenicity, virulence
Host factors - immunoresponses
What are the 3 main forms of the disease?
Visceral
Mucocutaneous
Cutaneous
What is the main species of Leishmania in Europe?
L. infantum
What is the epidemiology of the disease?
Dogs are the main reservoir and this can cycle between dogs and humans and dogs and sylvatic hosts.
Is there a group of people/animals that are most at risk to Leishmania?
Immunosuppressed individuals
What are the risk factors for human infection?
Increased prevalence in the dog population
Ownership of an infected dog (especially for transmission to children)
Poor socio-economic conditions (more likely to be close to dogs)
Dog density
What is the relationship between the type of immune response and the form of disease that develops?
Cellular –> subclinical or cutaneous
Humoral –> visceral
How have better HIV drugs impacted on Leishmania infections?
Reduced infection rate post HIV drugs.
How can you test for Leishmania infection?
By performing a skin test similar to that used for TB.
How else has the infection rate been reduced?
Filtration of donated blood and preventing donation from people from endemic areas.
Describe lesions seen in horses cause by L. braziliensis.
This disease is often self limiting and papulo-nodular lesions of the skin are seen. These are characterised by granulomatous dermatitis composed of giant cells.
How can leishmania amastigotes be visualised within cells?
They appear as dark staining intracellular points upon IHC staining.
Where does feline leishmaniosis occur?
It occurs sporadically in regions where canine leishmaniosis is endemic.
What type is seen?
Cutaneous or sub clin unless cats are immunosuppressed (e.g. FIV)=> visceral occurs.
What lesions are seen in the cutaneous form in cats?
Ulcercrusted dermatitis
Exfoliative alopecia
What is the role of cats and wild animals in the epidemiology of this disease?
It is not really known. It is possible that cats are underdiagnosed (as there is a high seroprevalence but low disease) and contribute to the epidemiology.
What is the relationship between leishmania of dogs in europe and in south america?
L. chagasis was found to be the same as L. infantum. European settlers likely brought the infection over with their dogs.
What is Mon-1 and where is it most prevalent?
It is a Leishmania enzyme isoform. It is most prevalent in Europe.
What breed of dogs in the USA seem most prone to Leishmania infantum?
Foxhounds
Where is this most prevalent in the USA?
On the east coast. This is where Lutzomyia is distributed
Has the role of Lutzomyia been verified?
No. Infection hasn’t yet been isolated in these animals so other forms of transmission may be important in these dogs.
Does infection always lead to disease?
No
Describe the relationships between seropositivity, cellular respiration and PCR positivity in clinical leishmaniosis, resistant and susceptible animals.
Resistant - variable serology, high cellular resp, PCR variable
Prone - seropositive with variable ABs, reduced cellular resp, PCR+
Disease - highly seropositive, reduced cellular resp., PCR+
How do these states of resistance/disease relate to the different types of immune response?
TH2 has high serology and low cellular killing and a high parasite load.
TH2 has low serology with good cellular immunity and low parasite load.
Other than dermatitis what is the clinical sign associated with Leishmaniosis?
Weight loss
Describe the initial stages in the pathogenesis of Leishmania infection.
Variable incubation period (can be >7years)…promastigotes penetrate cutaneous macrophages…replication…dissemination to other organs.
Describe the later stages in the pathogenesis of leishmaniosis.
B cells proliferate whilst T cells deplete
Lymphadenomegaly and splenomegaly occurs
Polyclonal antibody response
Hyperglobulinaemia but hypoalbuminaemia
What can immune complex formation lead to?
Glomerulonephritis
What causes epistaxis in a leishmania infection?
Thrombocyte destruction
Serum hyperviscosity due to hyperglobulinaemia
Ulceration of the nasal muscosa
What breeds are susceptible to Leishmaniosis?
GSD
Boxer
Rottweiler
How does the route of infection affect susceptibility to Leishmaniosis?
IV more susceptible to clinical (probably as more likely to be visceral) than sc infection.
What factors seem to affect transmission to the sandfly?
increased CD4+ count, negative serology and reduced sandfly result in reduced transmission to the sandfly.
How would the distinction between infected healthy and sick animals?
no clinical signs vs. clinical signs with the confirmed presence of infection.
What are the purposes (5) for which diagnosis can be performed?
- epidemiological studies
- blood donation
- screening clinically healthy dogs in endemic areas
- avoid importing infected dogs
- monitoring the response to treatments
What diagnostic approaches are there?
Clinicopathological findings
Specific tests
What classes of specific tests are there?
Parasitological
Serological
Molecular
Cellular immunity tests
What would be used in testing a:
a) sick dog
b) healthy dog
a) PCR
b) quantitative serology
What drugs are used to treat Leishmaniosis?
Meglumine antimoniate - anti malarial, unknown mechanism
Allopurinol - inhibits protein synthesis
Miltefosine - induces apoptosis somehow
allopurinol is often used in combination with the other two as it is longer acting
What are the prophylactic methods?
Insecticides - collars, spot ons, sprays
Vaccines - leishmune
best method is to use both!
When does the vector feed?
One hour before sunset to one hour after dawn - keep dog indoors at these times!
