Lecture 21- Leishmaniasis Flashcards
What is leishmaniasis?
Morbid and potentially fatal protozoan parasitic infection
Leishmaniasis is classified as what type of disease?
Classified as a neglected tropical disease (NTD)
What are the three clinical manifestations of leishmaniasis?
- Visceral Leishmaniasis (VL)
- Cutaneous leishmaniasis (CL)
- Mucocutaneous/mucosal leishmaniasis (MCL/ML)
Species are ____ restricted and outcome is determined by _______
- Geographically
- Host factors
Leishmaniasis is transmitted by what?
Female phlebotomine (old world) and Lutzomyia (new world)
What is the class, order and genus?
- Class = kinetoplastea
- Order = Trypanosomatida
- Genus = Leishmania
Who first described leishmaniasis in 1756?
Alexander Russell
The first species was describe by who?
Charles Donovan
What are the two important stages of leishmaniasis?
- Sandfly stage = promastigote
- Human stage = amastigote
Descibe the lifecyle of leishmaniasis
- The promastigote form is the flagellated form
- This stage is found in the sandfly
- When the sandfly takes a blood meal it injects the promastigote through the skin
- The promastigote gets phagocytised by the macrophages as part of the immune system
- Once engulphed by these cells transform into an amastigote and they lose the flagella and become round bodies
- Amastigotes is the stage found in human stage
- The amastigotes multiply in number and cause the cell to burst and disseminate into a number of different areas in the body
- The cycle repeats when sandfly takes its blood meal
- It reverts back to the promastigote stage
- They transform as they travel to the gut of the sandfly based on the nutrients present
- They are injected to the next mammal or human when the sandfly takes a blood meal
Why is species knowledge useful?
- Some go infect internal organs, some infect other areas of the skin
- It depends on the species type, they have different predilections for different parts of the bodies
- Different presentations are a result of different species
Why do you need to consider the role of the host immune response?
- So you know whether or not the macrophages can actually get rid of the parasite
- If immunocompromised, they can have more severe forms of the disease
What factors influence disease presentation?
- Disease presentation is multifactorial
- Species/geography
- Host immune response
- Virulence factors
- Location of sandfly bite
What species cause VL?
- L. donovani
- L. chagasi (NW)/ L. infantum (OW)
Where are the majority of cases found for VL?
Brazil, Ethiopia, India, Somalia, and Sudan
What allows for the transmission of VL in densly populated areas?
Animal reservoirs (canine population)
What is Post kala-azar dermal leishmaniasis (PKDL)?
- Complication of VL (6 months to 3 years) characterized by a maculopapular rash in patient previously recovered from VL caused by L. donovani
- Reoccurance of the disease
What are the symptoms of VL?
- Fever
- Weight loss
- Hepatosplenomagaly
- Anemia
- Thrombocytopenia
- Hypergammaglobulinemia
What is the most common form of leishmaniasis?
CL
Where is CL common?
Afghanistan, Brazil, Iran, Peru, Saudi Arabia, Syria
What species causes CL?
Caused by members of both old and new world leishmania complex and Viannia subgenus
Only a small fraction of those infected will develop _______
CL disease
What is the first sign of CL infection?
- Small erythematous papule
- First nodules, develops into ulcer, generally self-healing
What are some other forms/complications of CL?
- Disseminated leishmaniasis (DL)
- Diffuse CL (DCL)
- Atypical CL (ACL)
What is DL?
Macropapular skin lesions identified in 2 or more anatomical sites ranging from 10-300 in number
What is DCL?
Nodular, non ulcerative lesions on the face, limb and back
What is ACL?
- In those who are immunocompromised
- Unusual crusted, lupoid, sporotrichoid or verrucous ulcers
Where is VL commonly identified?
Latin America (Brazil, Peru, and Bolivia)
What is MCL/ML?
Sequela of the initial CL infection affecting mucous membranes of the upper respiratory tract
How does it get to the mucous membrane in MCL?
Through the lymphatic or haematogenous pathway
MCL is caused by what species?
Viannia subgenus
What plays a role in MCL infection?
Species, host immune response and endosymbiont Leishmania RNA virus-1/2 thought to play a role
What are the signs of MCL infection?
- First signs = nasal inflammation/stuffiness at first
- Followed by ulcerationof the nasopharyngeal mucosa
- Lastly, perforation of the septum
- Susceptible to secondary bacterial infections
What is the difference between old world and new world?
- Old world = found in Asia, Africa, Middle East
- New world = Viannia subgenus
What is Th1?
Pro inflammatory response
What is Th2?
Anti inflammatory response
What type of Th response does MCL have?
- Th1 response
- Low parasite burden
- Severe disease
What type of Th response does DCL have?
- High parasite burden
- Th2 response
- Severe disease
Describe the relationship between Th1 and Th2 response and disease severity
What markers are involved with Th1 response?
IFN-y, TNF-a, IL-12, IL-23, IL-27 (overexpression)
What markers are involved with a Th2 response?
IL-4, IL-6, IL-13, IL-10
What are some key virulence factors?
- Kinetoplastid membrane protein -11 (kmp-11)
- Lipophosphoglycans
- Heat shock proteins (HSPs)
- Cysteine peptidase (CPs)
- Host factors
- A2 protein
What is the virulence factor Kinetoplastid membrane protein -11 (kmp-11)?
- Modulate host immune response, reducing NO production
- Parasite uses it to its benefit to reduce the amount of NO produced within the macrophages to prevent it from being killed and allowing it to survive better
What is the virulence factor Lipophosphoglycans?
- Involved in sandfly stage for attachment, differentiation and growth
- Heavily in the promastigote stage
- They are upregulated in the sandfly to allow them to grow better
What is the virulence factor Heat shock protein (HSP)?
- Provide thermotolerance during differentiation phase
- Allow to tolerate changes in temperature
- Sandfly temperature 22-26C and the human body is 36C
- Increases when a promastigote enters the human body
What is the virulence factor Cysteine peptidase (CP)?
- Expressed during amastigote stage
- Involved in evading the immune response, prevent the killing of the parasite
What is the virulence factor host factors?
- MMP-9 involved in adherence for migration (allowing to stick to skin), phosphoprotein phosphatases (PPS), metal dependent protein phosphatases (PPMS) involved in producing antileishmanial molecules
- Allow to enter the host
What is virulence factor A2 protein?
- Only found in visceralizing species (protection against temperature stress)
- Believed to have a role in developing those more severe clinical manifestations
- Evaluated as a vaccine target now for VL
True or False? There is a difference in the number of chromosomes for new world and old world leishmaniasis
True
Are microscopic examinations available?
Yes for biopsies, aspirates, scrapings, impressions or cultures
What are the three stains available for microscopy?
- Giemsa stain
- Amastigotes
- Promastigotes
Serology is limited to?
VL
What types of serology tests are available for VL?
- ELISA/EIA
- IFA
- DAT
Treatment is complicated and limited to _____
Expensive drugs with substantial toxic effects
What is recommended in addition to therapy?
Wound care
Clinical resolution does not equal _______
Parasitological cure (can remain dormant)
