Leishmaniasis Flashcards
Classification of lesihmania
Genesis of protozoan parasites, come under kinetoplastids order
all members of order have kinetoplast
- dense granule of DNA, formed from mini and maxi circles
What are the three kinetoplastid diseases?
- Leishmania - sand fly vector
- Chagas disease - triatomine bug vector
- African sleeping sickness - tsetse fly vector
How is leishmania transmitted?
Female sand flies, two genera that transmit in different geographical locations
- phlembotomus spp. - transmits in old world, africa, eastern europe, middle east, central asia
- lutzomyia spp - new world
transmission when taking blood meal, can transmit bartonella and other viruses too
Life cycle of female sand fly
Transmission occurs during vector feeding
Promastigotes are phagocytosed by macrophage
Promastigote differentiates into amastigote inside macrophage
Reproduces asexually in vacuole
Amastigotes multiply in parasitophorous vacuole
Sand fly becomes infected when taking a blood meal from infected human (or other mammal) - takes up amastigote
In the midgut of the sand fly amastigotes transform into flagellated promastigotes and divide and migrate into salivary glands of the fly
Can take from 1-2 weeks, fly can once again infect hosts
Disease manigestations are caused by different leishmania species
Visceral leishmaniasis (VL)
- Leishmania donovani
- Leishmania infantum
Post-kala-azar dermal leishmaniasis (PKDL)
- Leishmania donovani
Cutaneous leishmaniasis (CL)
- Localised or simple – L.major, tropica, mexicana, braziliensis
- Mucosal leisons (ML) - L.aethiopica
- Diffuse (DCL) - L.mexicana, L.aethiopica
- Recidivans (LR) - L.tropica
Mucocutaneous leishmaniasis (MCL) - L.Viannia sub-genus
Describe VL
Most severe and systemic disease manifestation
- Fatal if untreated, 30,000 deaths per year
- Disease onset from 2 weeks to 6 months following an infectious bite
- Also known as kala-azar – black fever
- Identified in 1903 by Leishman and donovan
Signs and symptoms
- Fever
- Weight loss
- Anaemia
- Hepatosplenomegaly
VL primarily caused by two leishmania species
- Leishmania donovani – OW
- And leishmania infantum – OW and NW - domestic dogs
Describe post-kala azar dermal leishmaniasis (PKDL)
- Complication of following infection by L.donovani or L.infantum
- Important reservoir of infection
Can present in either macular or papular form
Can affect person’s quality of life.
Lesions are infections to the sand fly, where if blood meal is taken from around the edges of the lesions, the sandfly will take that up and pass it onto other hosts.
Disease is similar to leprosy, distinguished from leprosy as patient retains sensation to lesions.
Describe cutaneous leishmaniasis
Majority of leishmania cases
Also known as oriental sore
0.7-1 million new cases a year
Non-fatal
- Cosmetic morbidity
- Socially stigmatising
- Psychological effects
- L.tropica, major, aethiopica OW
- mexican and amazonensis NW
- surface lesions on oral/nasal/genital mucosa, not to be confused with MCL
Lesion form at bite site unlike VL where parasites migrate from bite site
localised or diffuse, begin with single nodule, spread to cover large parts of skin
Describe mucocutaneous leishmaniasis (MCL)
Invasive sequelae of CL – 1-10% cases
Caused primarily by species of leishmania Vianna sub-genus
- L.V. brazilienesis
- L.V. panamensis
- L.V peruviana
- L.L aethiopica
Life threatening
Permanent disfigurement
Describe leishmaniasis recidivans
Rare complication of CL
L.tropica, major and braziliensis
Reappearance of lesion sometimes years later
Indoor residual spraying IRS
- Primary vector control
- Coat inner walls of house with insecticide
- Done twice a year
- Commonly used for control programmes for other vector borne diseases
- There is DDT resistance so different class used
Most african leishmania vectors endophagic, feed outside, IRS not effective
Bed nets
More common for malaria but sandflies are smaller than mosquitoes so need nets with smaller mesh size
Nets coated with insecticide and a different class of insecticide to that used for IRS, used together to reduce emergence of resistance
What is the gold standard for diagnosis of VL?
Leishmania has non specific signs and symptoms
Gold standard is observation of parasites by microscopy
- Either splenic or bone marrow aspirate from patient, stained and identified under microscope
- Or lesion biopsy for CL
aspiration of lesion (CL)
or bone marrow (VL)
What are the disadvantages of using the gold standard?
- Poor sensitivity
- Require skilled microscopist to do diagnosis and trained healthcare professional to take clinical sample and facilities
- not suitable for remote field use
Diagnostics - splenic aspirate
Stain with giemsa stain
can’t speciate between leishmania with this approach
Serological assays for leishmania and their advantages/disadvantages
Either detects anti-leishmania antibodies or antigen from a clinical sample
Advantage compared to microscopy is you don’t need splenic or bone marrow aspirate or skilled microscopist to identify parasite
Cheap and easy to use
Not used for CL, often used to support VL diagnosis
Can be less sensitive and specific compared to gold standard
Varies in different regions, parasites and populations
Less sensitive in patients with HIV, especially if HIV predates leishmania
KAtex and Kalazar test
KAtex - antigen detection
- Leishmania antigen detected in urine using antibody coated latex beads
Kalazar - antibody detection
- detection of antibodies against recombinant product of 39 aa antigen encoded by kinesin-like gene of leishmania donovani complex
- low sensitivity in east africa where lower levels of anti-kinesin antibodies are seen
Leishmania skin test
Uses preserved promastigotes as antigen
Gives a delayed type hypersensitivity (DTH) reaction after 48-72 hours positive after cured VL
Useful in epidemiological surveys, used to determine cutaneous leishmaniasis exposure.
Also known as Montenegro test
e.g someone has suspicious skin lesions, can do this test to rule out CL
Disadvantage of this is that you need to culture parasites for the test and require facilities and personnel to do this.
And comes up positive for past infection.
Nucleic acid tests for leishmania
PCR amplification of either kinetoplast DNA or 16s rRNA
Identification to species level, identifying leishmania DNA
Use of primers specific for 16s rRNA or kinetoplast DNA
Highly sensitive
Expensive, need equipment
Used in eastern Europe and parts of middle east – L.infatum
Travel clinics
Not yet widely in field
Point of care device – next gen diagnostics
Treatment of CL, 1st and 2nd line drugs
1st line – pentavalent antimonials
2nd line - systemic
- Amphotericin B
- Pentamidine
- Miltefosine
Local
- Paromycin
- Thermotherapy
Challenges of treating CL
CL estimated one million cases worldwide, major outbreaks in Syria, afghanistan, ethiopia
Self-curing 3-18 months in 95% cases but disfiguring
Cochrane analyses in 2007 and 08 showed deficiency in treatments and in clinical studies
Not on the agenda of funders – a real NTD
TT4CL-SGUL coordinated H2020 funded project to develop new drug, D121, for CL
Vaccine for leishmaniasis
No fully licensed vaccine
Several in clinical and pre-clinical development
Reservoirs –canine vaccine used in south america on dog
Leishmanisation - vaccination done in middle eastern countries. Take parasites scraped from cutaneous lesion, inoculate them somewhere isn’t visible on patient, e.g back of leg, effectively lets you control where lesion and scar would form. Avoid face at all costs.
