Leishmania

PARASITES PROTOZOA

Leishmania

Leishmania Life Cycle - Wikimedia Commons

Leishmania donovani in bone marrow cell - Dr. L.L. Moore, Jr.

L. tropica - Yutaka Tsutsumi, M.D., Professor, Department of Pathology, Fujita Health University School of Medicine

• Leishmania spp. are intracellular parasites of macrophages

• Are closely related to Trypanosoma spp.

• Cause diseases in humans, dogs and wild animals

• Present in southern Europe, Africa, Asia and south America

• Can cause both cutaneous and visceral diseases

Recognition

• Ovoid shaped

• Possesses a rod-shaped kinetoplast

• Has a rudimentary flagellum which does not project beyond the cell margin

• After the amastigote has transformed into a promastigote inside the sand fly, the kinetoplast is situated in the posterior of the body

Life Cycle

• Transmitted by blood sucking sand flies
  • Phlebotomus spp. in the Old World
  • Lutzomyia spp. in the New World

• The amastigote (morphological form) is found in vertebrate macrophages

• Ingested by sand fly during feeding
  • Transforms in insect gut

• Multiplies and migrates to insect proboscis
  • Inoculated during feeding
  • Can be transmitted percutaneously if sand fly crushed on skin

• Invades macrophages and reverts to amastigote

• Multiplies by binary fission

Pathogenesis

• Infection of vertebrate host
  • Produces foci of proliferating Leishmania-infected macrophages in skin (cutaneous) or internal organs (visceral)

• Very long incubation period
  • Months to years

• Many infected dogs are asymptomatic

• Cutaneous form
  • Produces areas of ulceration on pinnae of ears, eyelids or on the lips

• Visceral form causes chronic wasting condition
  • Generalised eczema
    • Loss of hair around eyes producing 'spectacle' effect
  • Intermittent fever
  • Generalised lymphadenopathy

• Long periods of remission followed by recurrence of clinical signs is not uncommon in infections

• Involved in skin infections

Epidemiology

• Disease dependent on sand fly vectors
  • E.g. Common in dogs around the Mediterranean coast, foci around southern Europe and around Madrid

• Reservoirs of infection
  • E.g. Wild animals such as rodents and stray dogs

• Mechanisms of transmission
  • sand fly bite
  • Rarely through direct contact

• Leishmaniasis in British dogs
  • Susceptible to infection if exposed whilst abroad in endemic areas as have no immunity
  • No sand flies in Britain but dogs have become infected whilst in contact with infected imported animals

Diagnosis

• Demonstrate Leishmania organisms
  • In skin scraping or smears
  • In joint fluid, lymph node or bone marrow biopsies

Treatment and Control

• Chemotherapy
  • Prolonged treatment, expensive, suppresses infection
  • Does not cure infection

• Prevent sand flies biting
  • Collars, sprays containing insecticide with repellent effect

• Destruction of infected and stray dogs
  • Sand flies biting infected dogs may spread the disease to other dogs, humans and wildlife
  • There is a slight possibility of transmission to humans by direct contact

Trypanosoma

Trypanosoma cruzi - CDC/Dr. Myron G. Schultz

T. cruzi in monkey heart - Dr. L.L. Moore, Jr.

T. cruzi Life Cycle Diagram - Wikimedia Commons

Triatoma infestans the Kissing bug - WHO Wikimedia Commons

Chagas endemic zones 2005 - Wikimedia Commons

N'dama - Trypanotolerant West African Bos taurus - Wikimedia Commons

• Protozoal parasites found in the blood and tissues of vertebrates

• Worldwide distribution

• Causes sleeping sickness in humans

• Particularly seen in sub-Saharan Africa
  • Affects cattle production
  • Causes Nagana (Wasting disease)

• Divided into two groups depending on the mode of development in the insect vector
  • Salivarian
    • Multiply in the foregut and proboscis
    • Transmitted via inoculation during feeding
    • Transmitted by Tsetse flies
    • Also known as anterior station development
  • Stercorarian
    • Multiply in the hindgut
    • Infective form migrates to the rectum
    • Transmitted via contamination of wounds with insect faeces
    • Also known as posterior station development

• All Trypansomes except for T. equiperdum have arthropod vectors
  • T. equiperdum is a venereally transmitted disease

• Non-cyclical transmission can also occur
  • Mechanical transmission
  • Transferred by interrupted feeding from one host to another
  • Usually transmitted by biting flies, e.g. Tabanidae and Stomoxys

Recognition

• Elongated, spindle shaped protozoa

• Between 8 and 39 μm in length

• Flagellate
  • Flagellum runs the length of the body attached to the pellicle which forms an undulating membrane

• Kinetoplast present which contains the DNA of the single mitochondrion

Life Cycle

• Undergo morphological transformations in intermediate host before becoming infective for the next host

• Blood-sucking flies ingest trypanosomes whilst taking a blood meal from an infected animal
  • Trypanosomes multiply first in the gut of the fly

• Salivarian trypanosomes are transmitted by Tsetse flies
  • Trypanosomes pass forward to the salivary glands where they transform into the infective stage
  • Inoculated with saliva when Tsetse fly next feeds on a host

• Stercorarian trypanosomes are transmitted by triatomid bugs, tabanids and keds
  • Trypanosomes pass back to the rectum
  • Next host is infected when skin wounds are contaminated with infected insect faeces

Pathogenesis

• Salivarian
  • Causes wasting disease in cattle (nagana)
  • Sleeping sickness in humans

• Stercorarian
  • T. cruzi most important in veterinary medicine
    • Occurs in South America
    • Infects armadillos, possums and humans
    • Causes Chagas' Disease
  • Transmitted by a triatomid (kissing) bug
  • Chronic infections are often fatal causing heart failure
  • Non-pathogenic species are transmitted by tabanids and keds
    • T. theileria and T. melophagium

• Enlarged lymph nodes and spleen
  • Causes lymphoid exhaustion
  • Associated with plasma cell hypertrophy and hypergammaglobulinaemia
    • Due to an increase in IgM
  • With infections of increased duration, the lymph nodes and spleen shrink due to exhaustion of their cellular elements

• Anaemia
  • Red blood cells are removed from circulation (haemolytic)
  • Is a cardinal feature of the disease

• Degeneration and inflammation of multiple organs
  • E.g. Skeletal muscle, myocardium and CNS

Clinical Signs

• In ruminants:
  • Anaemia
  • Enlargement of the lymph nodes
  • Progressive loss of body condition
  • Fever and appetite loss occur during parasite peaks
  • Chronic disease usually terminates in death of the animal if untreated
  • Can cause abortion, infertility and decreased growth in herds

• In horses:
  • Acute or chronic infections of T. brucei
  • Oedema of the limbs and genitalia

• In pigs:
  • T. congolense infections are mild or chronic
  • T. simiae infections are hyperacute usually leading to death from pyrexia in a few days

• In dogs and cats:
  • T. brucei and T. congolese
  • Acute infections
  • Fever, anaemia, myocarditis, corneal opacity
  • Occasionally neurological signs present, such as increased aggression, ataxia and convulsions

Epidemiology

• Vector distribution
  • Tsetse flies found in riverine, savannah and forest habitats
  • Up to 20% flies infected
  • Flies infected for life

• Parasite virulence
  • Some parasitaemic animals survive for long periods of time
    • E.g. T. brucei and T. congolense
    • Increases the opportunity for infection of flies
  • Some trypanosomes kill their host in 1-2 weeks
    • E.g. T. vivax
    • Decreases the chances of fly infection
  • Trypanosomes avoid host immune defences by altering glycoprotein coat (surface antigen) before host antibody response
    • Antigenic variation can occur many times over several months causes relapsing parasitaemia

• Host response
  • Trypanotolerant wild animals remain parasitaemic for prolonged periods without showing clinical signs of disease
    • Cause lasting reservoirs of infection
  • Most domestic livestock are susceptible to trypanosomosis
  • Some local breeds of sheep, goats and cattle are trypanotolerant
    • E.g. Bos indicus

Diagnosis

• Demonstrate trypanosomes in blood
  • Giemsa stained smears
  • Fresh blood films
    • Motile trypanosomes
  • Haematocrit tube
    • Motile trypanosomes at the plasma/buffy coat interface

Control

• Tsetse fly control
  • Spraying and trapping

• Prophylactic drug treatment
  • Change drug group periodically to decrease the chances of resistance occurring
  • May lead to protective immunity but livestock will still be susceptible to heterologous challenges

• Barrier fences and buffer zones
  • Separate livestock and wild animals

• Trypanotolerant livestock

Other trypanosomes

• Mechanically transmitted by biting flies
  • E.g. Surra affecting horses and camels in North Africa, Asia and South America
  • T. equinum in South America
  • T. evansi in Asia

• Venereally transmitted
  • E.g. Dourine
    • Transmitted by T. equiperdum
    • Causes genital and abdominal oedema, emaciation and CNS signs
    • Affects horses and donkeys in Africa, Asia, Central and South America

• Non-pathogenic species occur in the UK
  • In sheep caused by T. melophagium
  • In cattle caused by T. theileri