Leishmaniases

 Leishmania tropica complex

 Leishmania mexicana complex
 Leishmania braziliensis complex
 Subgenus : Viania
 Leishmania donovani complex
Phylum : Sarcomastigophora

Subphylum : Mastigophora
Class : Zoomastogophoria
Order : Kinetoplastida
Family : Tryposomatidae
Genera : Trypanasoma
Leishmania
 Parasites Classifications
Phylum Subphylum Class Order Genus

Sarcomastigo Sarcodina Rhizopoda Amoebida Entamoeba

phora Acanthamoeba
(Amoeba and
flagellates) Naegleria

Balamunthia

Mastigophor Zoomastigo Kinetoplastida Leishmania

a phorea
Trypanosoma

Diplomonadida Giardia

Trichomonadida Dientamoeba

Trichomonas

Ciliophora Kinetofragminoph Trichostomatida Balantidium

orea
 Leishmaniases - The Diseases Burden

 350 Million People at Risk

 An estimated 2 million new cases annually
20, 000 – 30, 000 Deaths annually
Leishmaniases – The Diseases

3 main forms of the disease:-

 Visceral Leishmaniasis (Kala-azar) - The Most Serious
 500, 000 new cases worldwide annually
 Over 90% of new cases occur in 6 countries: Bangladesh, Brazil,
Ethiopia, India, South Sudan and Sudan
 10% Elsewhere, including Africa (Kenya)
 Post-Kala-azar dermal leishmaniasis (PKDL)
 It occurs mainly in East Africa and on the Indian Subcontinent
 Cutaneous Leishmaniasis - The Most Common
 95% of cases occur in the Americas, the Mediterranean basin, East
Africa; the Middle East and Central Asia
 Elsewhere : Afghanistan, Algeria, Brazil, Colombia, Iran and the Syria
 0.7 - 1.3 Million new cases occur worldwide annually
 Mucocutaneous Leishmaniasis
 A complication of CL
 90% of cases occurs in Bolivia, Brazil and Peru
 Leishmaniases - Geographical Distribution
The Old World (Eastern Hemisphere):-
 Asia
 The Middle East
 Africa (particularly in the Tropical region and North Africa, with some
cases elsewhere)
 Southern Europe
 It is not found in Australia or the Pacific islands
The New World (Western Hemisphere):-
 Mexico
 Central America
 South America
 It is not found in Chile or Uruguay
 Occasional cases of Cutaneous Leishmaniasis have been acquired in Texas
and Oklahoma;
Anthroponosis (some species) - No other mammalian reservoir host
other than human, e.g. L.donovani; L. tropica
Zoonotic (most species) - Various animals are reservoirs, like Dogs; Rats;
Gerbilas; Squirrrels; Monkeys, and Raccoons;
 Phylum : Athropoda

Class: Insecta Class: Insecta Class: Insecta

Order: Diptera Order: Hemiptera Order: Diptera

Family: Muscidae Family: Reduviidae Family: Psychodidae

Genera: Glossina Genera: Triatoma Genera: Phlebotomus

: Rhodnius : Lutzomiya
: Panstrongylus
: Eutritoma
 Leishmania Vectors - Geographical Distribution

Leishmaniases are vector-borne diseases that are transmitted

by Female Sandflies belonging to esp. 2 Genera:-
Phlebotomine (Old World)
Lutzomiya (New World)
 Important Sand fly Species
Region/country Vector spp. Disease type

Argentina/Mexico Lutzomyia longipalpis Cutaneous/visceral

Mexico L. olmeca Cutaneous

Panama L. panamensis Cutaneous

Brazil L. whitmani/intermedia Cutaneous

Columbia L. evansi, gomezi Cutaneous

Venezuela L. vallesi, gomezi Cutaneous
Phlebotomus langeroni
Sudan Visceral
orientalis

Kenya/Ethiopia P. martini Visceral

N. W. Africa P. dubosqi Cutaneous

Egypt P. langeroni Visceral
 Important Sand fly Species
Region/country Vector spp. Disease type

Palestinian W. Bank Phlebotomus papatasi Cutaneous

P. sergentii Cutaneous
P. syriacus Visceral
Greece P. neglectus Visceral
India P. papatasi Cutaneous
P. argentipes Visceral
Saudi Arabia P. papatasi Cutaneous
Monaco P. perniciosus Visceral
P. ariasi Visceral

China P. alexandri Visceral

P. chinensis Visceral
P. longiductus, Visceral
Phlebotomine Sand fly
Phlebotomine Sand flies
Morphological types of Haemoflagellates
 Leishmania species - Morphology Forms
 All Leishmania species exist in two forms:-
Amastigote – both in Vectors and Mammals
Promastigote - both in Vectors and Mammals

 Leishmania donovani:-
 Amastigotes
 ovoid;
 rounded body;
 measuring about 2-3μm in breadth;
 Promastigotes
 Elongate
 measuring about 5 - 25μm length x 1.5 - 3.5μm breadth
 Important Leishmania Species and The Clinical Disease they Cause

Clinical Disease Leishmania Species Geographical

Location

1.Cutaneous L. tropica complex L. tropica Old World

L. major
”
L. aethiopica ”
L. mexicana complex L. mexicana New World
L. amazonensis ”

L. venezuelensis ”

L. braziliensis complex L. (V.) braziliensis New World

*subgenus Viannia
L. (V.) guyanensis
”
L. (V.) panamensis ”
L. (V.) peruviana ”

L. donovani complex L. infantum Old World

L. chagasi New World

 Important Leishmania Species and The Clinical Disease they Cause, continued

Clinical Disease Leishmania Species Geographical

Location

2. Mucocutaneous L. braziliensis complex L. (V.) braziliensis New World

L. (V.) guyanensis
”
L. (V.) panamensis ”
L. (V.) peruviana ”

L. mexicana complex L. mexicana New World

L. tropica complex L. tropica Old World

L. major
”
3. Visceral L. donovani complex L. donovani
”
L. infantum ”
L. chagasi New World

L. tropica complex L. tropica Old World

L. mexicana complex L. amazonensis New World

 Leishmania Species - Life Cycle
 Leishmaniasis is transmitted by the bite of infected Female Phlebotomine (OW) or
Lutzomiya (NW) Sandflies
 The sandflies inject the Infective Stage, Metacyclic Promastigotes, into a host during
feeding
 Promastigotes are phagocytized by Macrophages; Dentritic Cells; Other Mononuclear
Phagocytic Cells
 Phagolysosome biogenesis is inhibited by the Promastigote Surface Lipophosphoglycan
 Promastigotes transform intracellularly into the tissue stages of the parasite,
Amastigotes
 Amastigotes in tissues multiply several times by Simple Binary Fissions
 Amastigotes then invade more Mononuclear Phagocytic cells; Macrophages; & …………
 Depending of Leishmania specie, the infection becomes Symptomatic:-
 Cutaneous Leishmaniasis
 Mucocutaneous Leishmaniasis
 Visceral (Kala-azar) Leishmaniasis
 Sandflies become infected by ingesting Infected Cells/free Amastigotes during blood
meals
 In Sandflies, Amastigotes transform into Promastigotes, which multiply by longitudinal
binary fissions:-
 in the Hindgut for Leishmanial organisms in the Viannia subgenus
 in the Midgut for other Leishmania genera
 Infective Metacyclic Promastigotes then migrate to the Anterior Midgut/Thorax/
Proboscis in readiness for transmission during the Sandflies’ next feeding
Life Cycle - Leishmania Species
Other Transmission Modes

 Mechanically through biting flies like Stomoxys. All types.

 Blood Transfusion from the infected Monocytes. All
types.
 Organ Transplants for Visceral Leishmaniasis
Leishmaniases – The Diseases

3 main forms of the disease:-

 Visceral Leishmaniasis (Kala-azar) - The Most Serious
 500, 000 new cases worldwide annually
 Over 90% of new cases occur in 6 countries: Bangladesh, Brazil,
Ethiopia, India, South Sudan and Sudan
 10% Elsewhere, including Africa (Kenya)
 Post-Kala-azar dermal leishmaniasis (PKDL)
 It occurs mainly in East Africa and on the Indian Subcontinent
 Cutaneous Leishmaniasis - The Most Common
 95% of cases occur in the Americas, the Mediterranean basin, East
Africa; the Middle East and Central Asia
 Elsewhere : Afghanistan, Algeria, Brazil, Colombia, Iran and the Syria
 0.7 - 1.3 Million new cases occur worldwide annually
 Mucocutaneous Leishmaniasis
 A complication of CL
 90% of cases occurs in Bolivia, Brazil and Peru
 Clinical Features
1. Visceral Leishmaniasis (Kala-azar)
 Is Fatal (within 2 Years), Mortality ranges, 75 to 95%
 The illness typically develops within months after the sand fly bite
 Affects Several Internal Organs, especially the Reticuloendothelial
System (Spleen, Liver, Bone-marrow)
 It is characterized by:
Irregular Fever
Weight loss
Enlargement of the internal organs – esp. Splenomegally;
Hepatomegally
Lymphadenopathy
Anaemia (Severe)
Leukopenia
Thrombocytopenia
Pedal Oedema
Dysentery
Congestive Heart Failure (Tachycardia)
 Clinical Features
Post-Kala-azar Dermal Leishmaniasis (PKDL)
 It’s a Result of Previous Visceral Leishmaniasis
 It occurs mainly in East Africa and on the Indian subcontinent, where up
to 50% and 5–10% of patients with kala-azar, respectively, develop the
condition
 It usually appears 6 months to 1/or More Years after kala-azar has
apparently been cured
 People with PKDL are considered to be a potential source of Kala-azar
infection
 BUT, Clinical Manifestations:-
Macular/Papular or Nodular rash
Esp. on face, upper arms, trunks and other parts of the
body
 Host – Parasite Relationship; & Pathogenesis
(Cutaneous Leishmaniasis)

 The vector inoculates Metacyclic Promastigotes

 Promastigotes differentiate to proliferative Amastigotes in immediate
Cutaneous Tissues, esp.
 Macophages
 Endothelium of Blood Vessels
 Granulomatous reactions & formation of Nodules
 The parasites prefers Endothelial cells of the Capillaries of the infected
sites
 Disrupted blood supply & Parasite damage to Capillaries Endothelial Cells
 Ulceration of Nodules
 Enlargement of regional Lymph Nodes
 Resistance to Re-infection by the same Specie is Good (nearly Absolute)
 Example:-
 Infection with L. major protects subsequent infection with L. tropica
 BUT, Infection with L. tropica doesn’t confer immunity to subsequent
infection with L. major
 Clinical Features

The most common form of Leishmaniasis

2a. Cutaneous Leishmaniasis
2b. Diffuse Cutaneous Leishmaniasis – More Severe
It causes skin lesions, mainly ulcerations:-
The Sores typically develop within a few weeks or months
after the sand fly bite
The sores may start out as red papules (bumps) or nodules
(lumps) at site of fly’s bite
 Necrosis and Ulcerations
Skin ulcers might be covered by Scab or Crust
(Hyperkeratosis) which is usually followed by The sores
usually are painless (but can be painful)
Other Species related Clinical Differentiations
Cutaneous Leishmaniasis (Oriental Sore, Old World)
Caused by Leishmania tropica complex
 L. tropica produces Chronic Disease – Lasts for a Year or Longer, if not
treated
 Dry lesions, ulcerate after several months
 Usually Single lesions & primarily on the Face
 Mostly in Urban Areas, esp. prevalent in Mediterranean region; and
Kenya
 L. ethiopica characteristically similar to L. tropica
 Prevalent in Ethiopia & Kenya
 L. major produces an Acute Disease – duration 3 to 6 months
 Lesions primarily on Lower Limbs
 Lesions are Moist and ulcerate early
 Can have secondary/satellite lesions
 Mostly in Rural Areas, esp. Egypt; Sudan; some Northen & West
African Countries
Active Cutaneous Leishmaniasis lesion
Clinical Features

3. Mucocutaneous Leishmaniasis (Espundia, Uta, Chiclero Ulcer)

 A less common form of leishmaniasis
 Can be a sequel of infection with some species that cause Cutaneous
Leishmaniasis
 After a Sand fly bite, a granulomatous response occurs, and a necrotic
ulcer forms
 The lesions tend to become superinfected with bacteria
 Lesions begin to spread on the skin as well as in mucous membranes and
cartilage:-
 Mucous membranes of the nose - most common location
 Mouth, throat, pharynx, and larynx
 The spread is initially by direct extension and later by by metastasis
 Regional Lymphadenopathy is common
 Extensive Disfiguring of the Nasal Septum, Lips, and Palate
 Symptoms of nasal obstruction and Bleeding
 Leads to total destruction of mucous membranes of the nose, mouth and
throat
Mucocutaneous Leishmaniasis
Diagnosis
Laboratory Methods
 Microscopy:-
 To detect the parasite
 To identify the Leishmania species
Tissue specimens needed:-
 Skin Sores - for Cutaneous Leishmaniasis
 Bone Marrow - for Visceral Leishmaniasis
 Others biopsies like Spleen; Lymph Nodes – for Amastigotes
appearing intracellularly & extracellularly

 Serology – To detect Antibodies to the parasite (FAT)

 Others:-
 Travel history, in combination with clinical presentation
 Xenodiagnostic with a hamster using biopsy specimen of ulcer
 PCR Techniques
Light-microscopic examination of a stained bone marrow specimen from a
patient with visceral Leishmaniasis - Macrophage containing
multiple Amastigotes
Treatment
 Before considering treatment, the first step is to make sure
the diagnosis is correct
 Treatment decisions should be individualized
 Factors to consider include:-
Leishmania species
The potential severity of the case
Patient's underlying health
 The best way to prevent Mucosal Leishmaniasis is to ensure
adequate treatment of the Cutaneous infection
 If not treated, severe (advanced) cases of Visceral
Leishmaniasis are fatal
Treatment - Visceral Leishmaniasis
Parenteral Therapy
 Liposomal Amphotericin, 3–5 mg/kg IV, 3–5 days up to
cumulative dose of 15 mg/kg or single 10 mg/kg IV dose
 Pentavalent Antimonials:-
 Sodium Stibogluconate 20 mg/kg/day, IV/IM x 28–30 days
 Meglumine Antimoniate 20 mg/kg/day, IV/IM x 28–30 days
 Amphotericin 0.5–1 mg/kg/day up to cumulative dose of 20–45
mg/kg
Oral Drug Therapy
 Miltefosine , 2.5 mg/kg/day, Adults 150 mg PO/day given as 50
mg 2–3 x/day x 28 days
Combination Therapy
 Amphotericin and Miltefosine combined
Treatment - Cutaneous Leishmaniasis
Local Drug Therapy
 Paromomycin ointment 15% -apply BID for 20–28 days
 Clotrimazole 1% /Miconazole 2% ointment applied BID x 30 days

Oral Drug Therapy

 Azoles:-
 Fluconazole, 400 mg PO, day x 6 weeks
 Ketoconazole, 600 mg PO, day x 6 weeks
 Itraconazole, 400 mg PO, day x 3–6 weeks
 Miltefosine, 2.5 mg/kg/day or Adults, 150 mg PO/day given as 50 mg 2–
3x/day x 28 days

Parenteral Therapy
 Pentavalent antimonials
 Amphotericin
 Liposomal amphotericin
 Pentamidine
Prevention and control

Requires a combination of intervention strategies:-

 Early diagnosis and effective Case Management - reduces
the prevalence of the disease
 Vector control - helps to reduce or interrupt transmission of
disease by controlling sandflies:-
insecticide spray
use of insecticide–treated nets
environmental management
personal protection
 Effective Disease Surveillance - Early detection and
treatment of cases helps reduce transmission and helps
monitor the spread and burden of disease
 Control of Reservoir Hosts
 Social Mobilization - education of the community with
effective behavioural change interventions