3. INTRODUCTION
Leishmaniasis refers to a diverse spectrum of clinical syndromes caused
by infection with protozoan parasites of the genus Leishmania.
Leishmania sp. belong to the order Kinetoplastida and the family
Trypanosomatidae which includes other parasites of mammals,
including humans (genus Trypanosoma).
4. INTRODUCTION
Clinical syndromes of leishmaniasis include:
Visceral leishmaniasis (VL)
Post kala azar dermal leishmaniasis (PKDL)
Cutaneous leishmaniasis (CL)
Diffuse cutaneous leishmaniasis (DCL)
Leishmaniasis recidivans (LR)
Mucocutaneous leishmaniasis (MCL)
5. CLASSIFICATION
Leishmania has two subgenera Leishmania Leishmania and Leishmania
Viannia.
The main difference between the two subgenera is that promastigotes
of the subgenus Viannia develop in the midgut and hindgut of the
insect vector whereas that of subgenus Leishmania develop in the
anterior portion of the alimentary tract of the sandfly.
10. INTRODUCTION
The genus Leishmania includes over 20 different species, the majority
of which commonly infect humans, in whom they are responsible for
various types of disease.
11. INTRODUCTION
All members of the genus Leishmania are obligate intracellular parasites
that pass their life cycle in 2 hosts, the mammalian host and the insect
vector (female sandfly). In humans and other mammalian hosts, they
multiply within macrophages in which they occur exclusively in the
amastigote form. In the sandfly, they occur in the promastigote form.
12. INTRODUCTION(Morphology)
There are two principal morphological stages: the intracellular
amastigote, within the mononuclear phagocytic system of the
mammalian host and the flagellated promastigote within the intestinal
tract of the insect vector.
The amastigote stage is a round or oval body about 2–6 μm in diameter,
containing a nucleus and a kinetoplast. The amastigotes multiply within
the macrophages.
The promastigote stage has a long and slender body (about 15–30 μm
by 2–3 μm) with a central nucleus, a kinetoplast and a long free anterior
flagellum.
15. EPIDEMIOLOGY
Leishmaniasis has an immense geographical distribution in the tropics
and subtropics of the world, extending through most of the Central and
South America, part of North America, central and Southeast Asia,
India, China, the Mediterranean region and Africa. India is the biggest
focus of Visceral leishmaniasis (VL) in the world. Presently, 90% of the
VL cases in the world are in Bangladesh, India, Nepal, Sudan and Brazil.
Leishmaniasis is part of the neglected tropical diseases and it’s is of
public health significance, especially in the North-West and North-East
Nigeria which forms the belt of the disease in the country.
16. EPIDEMIOLOGY
Old world leishmaniasis: Affects Asia, Africa and Europe and it is
transmitted by sandfly of the genus Phlebotomus.
New World Leishmaniasis: Affects Central and South America and is
transmitted by sandfly of the genus Lutzomyia and genus
Psychodopygus.
17. EPIDEMIOLOGY
The large majority of Old World Cutaneous leishmaniasis (CL) is due to
the two species Leishmania major and Leishmania tropica and
proceeds from countries such as Afghanistan, Iran, Saudi Arabia and
Syria. In the New World, Leishmania braziliensis is the species with the
widest distribution area. It extends from south of Mexico to north of
Argentina.
18. EPIDEMIOLOGY
The disease affects people of low socioeconomic status and it is
associated with malnutrition, population displacement, poor housing, a
weak immune system and lack of financial resources.
Leishmaniasis is also linked to environmental changes such as
deforestation, building of dams, irrigation schemes and urbanization.
An estimated 700,000 to 1 million new cases occur annually (WHO).
19. EPIDEMIOLOGY
Visceral leishmaniasis (VL) also known as kala-azar is fatal and has
emerged as an important opportunistic disease in persons with AIDS in
southern Europe and other areas of the world where the two diseases
coexist, in persons who have had organ transplants and in association
with other conditions in which cell-mediated immunity is compromised.
An estimated 50,000-90,000 new cases of VL occur worldwide annually.
20. EPIDEMIOLOGY
Cutaneous leishmaniasis is the most common form and causes skin
lesions on exposed parts of the body which can leave life-long scars. It is
estimated that 600,000 to 1 million new cases occur worldwide
annually. CL cases occur in the Americas, the Mediterranean basin,
Middle east and central Asia.
Mucocutaneous leishmaniasis affects the mucus membranes of the
nose, mouth and throat which leads to partial or total destruction of the
mucus membranes of these areas. Over 90% of MCL cases occur in
Bolivia.
21. Leishmania-HIV co-infection
People living with HIV and who are infected with leishmaniasis rapidly
progress to full blown disease, high relapse and mortality rates. As of
2021 Leishmania-HIV coinfection has been reported from 45 countries
with high co-infection rates reported from Brazil, Ethiopia and india.
23. Epidemiology
Most leishmaniases are zoonotic infections and the reservoir hosts are
various species of mammals which are responsible for the long term
maintenance of Leishmania sp. in nature. Depending on the focus, the
reservoir can be either a wild or a domestic mammal.
24. EPIDEMIOLOGY
Although most transmission is by sand fly bites; The infective stage is
the metacyclic promastigote. Leishmania can be transmitted by blood
transfusions, sharing of needles by intravenous drug abusers,
occupational exposures, congenital transmission and rarely by sexual
transmission.
25. EPIDEMIOLOGY(Life cycle)
The life cycle begins when the metacyclic promastigote, an elongate,
motile form of the parasite found in the sandfly digestive tract and
proboscis is transmitted into the skin of a mammalian host by the bite
of small, delicate female sand flies when they take a blood meal.
Metacyclic promastigotes transform into amastigotes in macrophages
where they multiply by simple binary division eventually rupturing the
cell and invading other reticuloendothelial (RE) cells. Released
amastigotes go on to infect other mononuclear phagocytes.
26. EPIDEMIOLOGY(Life cycle)
Amastigotes have a distinct, rod-shaped, red-staining structure called a
kinetoplast which is a specialized mitochondrial structure that contains
a substantial amount of extranuclear DNA.
27. EPIDEMIOLOGY(Life cycle)
Amastigotes disseminate through regional lymphatics and the vascular
system to infect mononuclear phagocytes throughout the
reticuloendothelial system. The cycle is completed when female
phlebotomine sand flies ingest amastigotes. When in the digestive tract
of the sand flies, Leishmania parasites develop through a series of
flagellated intermediate stages to become infectious metacyclic
promastigotes.
29. PATHOGENESIS
Within the dermis of mammalian skin, the metacyclic promastigotes
escape complement activation, with the aid of their surface
components, mainly lipophosphoglycan (LPG) and glycoprotein (gp 63)
and attach to macrophages. They are then phagocytosed by
macrophages within which they transform into amastigotes and have
the capacity to resist intracellular digestion.
30. Pathogenesis
Their survival in these cells is the result of several factors related to the
cell itself (decrease in the production of oxidative and nitrogenic
derivatives triggered by the presence of the parasite) and to the
amastigote’s ability to resist lysosomal hydrolases, a property probably
related to its surface components;The gp-63 antigen gives protection
from proteolytic enzymes secreted from the phagolysosome.
LPG is the principlal virulence factor, exhibits a variety of functions. It
prevents phagosome maturation and protects the parasite against
hydrolytic enzymes secreted from the phagolysosome.
31. Pathogenesis
The host immune response also plays a role. Depending on the host
immune response, the amastigotes are either killed or allowed to
multiply inside the macrophages. There are two extreme poles, each
which is characterized by one of the two type of T helper subset
responses, i.e. T helper 1 or T helper 2 responses. Th-1 response is
induced by interleukin-12 (IL-12) which leads to increase production of
interferon γ (IFN-γ) and IL-2. At the cellular level, IFN-γ activates
macrophages which in turn kill amastigotes by induction of nitric oxide
synthase and oxidative killing mechanisms. Individuals with this
response exhibit a delayed-type hypersensitivity (DTH) to leishmanial
antigens (positive leishmanin skin test).
.
32. Pathogenesis
Th-2 cells stimulation results in increased production of IL-10 and IL-4.
It is observed in patients that develop active VL and in diffuse CL. IL-10
inhibits macrophages to kill amastigotes by downregulating the
production of (TNF-α)and nitric oxide and this helps in enhanced
survival and growth of the parasite. Patients with the Th-2 response do
not show positive leishmanin skin test.
33. CLINICAL FEATURES
The clinical syndromes and manifestations of leishmaniasis are divided
into three :
Visceral leishmaniasis (VL): Most severe
Cutaneous leishmaniasis (CL): Most common
Mucocutaneous leishmaniasis (ML)
35. Leishmania parasites, clinical
syndromes and geog.distribution.
Species Disease Geog.dist Vector Reservoir
Leishmania
Leishmania
donovani
Visceral
leishmaniasis
(Kala azar
or
dumdum
fever)
Middle East,
Africa, and
Indian
Subcontinent
Phlebotomus
argentipes,
Phlebotomus
orientali
Humans
Leishmania
Leishmania
infantum
Visceral
leishmaniasis,
cutaneous
leishmaniasis
Mediterranea
n Coast,
Middle East,
and
China.
Phlebotomus
Perniciousus,
Phlebotomus
ariasi,
Phlebotomus
papatasi
Dog, fox,
jackal, and
wolf
36. Leishmania parasites, Clinical
syndromes and G.distribution.
Species Disease Geog.distr Vector Reservoir
Leishmania
Leishmania
chagasi
Visceral
leishmaniasis
Tropical South
America
Lutzomyia
longipalpis
Fox and wild
canines
Leishmania
Leishmania
tropica
Cutaneous
Leishmaniasis
(oriental sore,
Baghdad boil)
Middle East
and
Central Asia
Phlebotomus
sergenti
Humans
37. Leishmania parasites, Clinical
syndromes and G.distribution.
Species Disease Geod.distr Vector Reservoir
Leishmania
Leishmania
major
Cutaneous
leishmaniasis
Africa, Indian
Subcontinent,
and
Central Asia
Phlebotomus
papatasi,
Phlebotomus
duboscqi
Gerbil
Leishmania
Leishmania
aethiopica
Cutaneous
and
diffuse
cutaneous
leishmaniasis
Ethiopia and
Kenya
Phlebotomus
longipes,
Phlebotomus
pedifer
Hydraxes
38. Leishmania parasites, Clinical
syndromes and G.distribution.
Species Disease Geog.distr Vector Reservoir
Leishmania
Vianna
braziliensis
complex
Mucocutaneo
us
leishmaniasis
(Espundia)
Tropical South
America
Lutzomyia
umbratilis
Forest
rodents
and
peridomestic
animals
Leishmania
Leishmania
mexicana
complex
Mucocutaneo
us
leishmaniasis
(Chiclero’s
ulcer)
Central
America and
Amazon basin
Lutzomyia
olmeca,
Lutzomyia
fl airscutellata
Forest
rodents and
marsupials
39. OLD WORLD LEISHMANIASIS
L. donovani causes visceral leishmaniasis or Kala-azar. It also causes the
condition, Post Kala-azar Dermal Leishmaniasis (PKDL).
Sir William Leishman in 1900, observed the parasite in spleen smears of
a soldier who died of ‘Dumdum fever’ or Kala-azar contracted at Dum
Dum, Calcutta. Leishman reported this finding from London in 1903. In
the same year, Donovan also reported the same parasite in spleen
smears of patients from Madras.
40. OLD WORLD LEISHMANIASIS
Visceral leishmaniasis or Kala-azar is a major public health problem in
many parts of world. According to the WHO, a total of 50,000-90,000
cases of visceral leishmaniasis occur every year. Of these new cases,
90% are found in the Indian subcontinent, Sudan and Brazil.
41. Infantile visceral leishmaniasis
due to L. infantum
This form is predominant in the Mediterranean basin, where it was
described in 1908. In North Africa, the prevalence in young children
remains high. Affecting principally young children (3–5 years), it is
characterized by the classical symptomatic triad: fever, anaemia and
splenomegaly.
42. OLD WORLD LEISHMANIASIS
The amastigote /Leishman Donovan (LD body) of L. donovani is found in
the reticuloendothelial system. They are found mostly within the
macrophages in the spleen, liver, bone marrow and less often in other
locations such as skin, intestinal mucosa, and mesenteric lymph nodes.
43. OLD WORLD LEISHMANIASIS
The spleen is the most affected organ. It is grossly enlarged and the
capsule is thickened due to perisplenitis. The liver is enlarged. The
Kupfer cells and vascular endothelial cells are heavily parasitized. The
bone marrow is heavily infiltrated with parasitized macrophages, which
may crowd the hematopoietic tissues. Peripheral lymph nodes and
lymphoid tissues of the nasopharynx and intestines are hypertrophic.
Severe anaemia with hemoglobin levels of 5–10 g/dL may occur in Kala-
azar.
44. CLINICAL FEATURES OF VL
The onset is typically insidious. The clinical illness begins with fever,
which may be continuous or irregular.
Hepatosplenomegaly
Weight loss
Pallor
Weakness
Prolonged fever
Fatigue
Lymphadenopathy
46. Post Kala-azar Dermal
Leishmaniasis (PKDL)
PKDL appears after a latent period of approximately 1-2 years after kala-
azar cure in India, while in Sudan it can start before symptoms of kala-
azar have completely subsided. It begins as depigmented macules, the
PKDL skin lesions turn into papular, then nodular eruptions. Located
initially on the face and the upper limbs, they can extend to the whole
body surface. The lesions may resolve spontaneously within 6 months
or last for many months or years. They contain numerous parasites and
play an important role in transmission and parasite dissemination.
47. PKDL
The most important immunological feature in Kala-azar is the marked
suppression of cell-mediated immunity to leishmanial antigens. This
makes unrestricted intracellular multiplication of the parasite possible.
There is an overproduction of immunoglobulins.
50. NEW WORLD LEISHMANIASIS
Lindenberg and paranhos (1909) first described amastigotes in the
ulcers of skin in a man in Brazil. Vianna (1911) named the species as L.
braziliensis.
L. braziliensis complex and L. mexicana complex cause new world
leishmaniasis in Central and South America.
51. NEW WORLD LEISHMANIASIS
Amastigotes are found in the reticuloendothelial cells and lymphoid
tissues of skin, but not in the internal organs.
The infection is transmitted to man from animals by bite of sandfly
vectors of the genus Lutzomyia.
52. CUTANEOUS LEISHMANIASIS
(CL)
CL presents as skin lesions, which are generally localized, without the
involvement of mucosae and not generalized infections.
They occur on exposed parts of the body surface accessible to sandflies,
principally on the face, hands, forearms and lower limbs.
53. CLINICAL FEATURES OF CL
The cutaneous lesion starts as an erythematous papule, similar to an
insect bite. It regularly enlarges, reaching its definitive size in a few
weeks.
The mature lesion is well defined, with a regular outline, and generally
round or oval in shape
54. FORMS OF CUTANEOUS
LEISHMANIASIS
The various forms include:
Localized CL
Ulcerative lesions- L.major
Dry type- L.tropica
Diffuse CL- L.amazonensis, L.mexicana & L.aethopica
Leishmaniasis recidivans- L.tropica & L.brazilensis
59. Leishmaniasis recidivans
Leishmaniasis recidivans (LR) is usually associated with L. tropica
infection. It has been described across North Africa, the Middle East,
Turkey, Southwest Asia, and Iran. The lesions are often on the face and
consist of small papules that spread outward, leaving a scar at the
center. It is characterized by very few parasites with an intense cell-
mediated immune response.
61. MUCOCUTANEOUS
LEISHMANIASIS (MCL)
About 2% to 5% of persons infected with L. braziliensis, L. panamensis,
L. guyanensis, or L. amazonensis develop mucous membrane
involvement of the nose, oral cavity, pharynx, or larynx months to years
after their skin lesions have healed. Mucosal involvement usually occurs
following a resolved primary ulcer but occasionally is concurrent.
62. MCL
The initial symptoms of American mucosal leishmaniasis (ML) are often
nasal stuffiness, discharge, discomfort, or epistaxis. Over time, a small
nodule develops on the inferior turbinate or septum. Septal ulceration
occurs early and may progress to perforation and eventual destruction
of the septum, resulting in nasal collapse, sometimes called a “tapir”
nose.
63. MCL
When hypertrophy predominates, resulting in a protuberant nose and
lips, the condition is called espundia. Risk factors associated with the
development of ML are male gender, young adult age, severe
malnutrition, and duration of primary ulcer for more than 4 months.
65. Leishmaniasis with HIV co-
infection
Co-infection of HIV with leishmaniasis has been reported from more
than 35 countries. Leishmanial parasites appears to cause activation of
latent HIV. HIV causes activation of T helper- 2 cells response leading to
disease progression. HIV co-infected patients do not show the classical
signs of VL like hepatosplenomegaly; They present with atypical
features due to loss of immunity with presence of more gastrointestinal
tract (GIT) and pulmonary symptoms. CD4 T cell count often fall often
fall below 50/µL (almost always < 200/µL).
66. DIAGNOSIS
Microscopy: Demonstration of amastigotes in smears of tissue aspirates
is the gold standard for diagnosis of visceral leishmaniasis. For
microscopic demonstration of the parasite, the specimens collected are:
Splenic aspirate
Peripheral blood
Bone marrow aspirate
Lymph node aspirate
Biopsy of skin lesions for cutaneous leishmaniasis
67. DIAGNOSIS
The smears are stained with Leishman, Giemsa, or Wright’s stains and
examined under oil immersion objective.
Culture: Different tissue materials or blood are cultured on NNN (Novy-
MacNeal-Nicolle) medium. Schneider’s tissue culture medium can also
be used.
Animal inoculation: Hamsters are inoculated and examined for
amastigotes.
69. DIAGNOSIS
Serodiagnosis: Detection of antigens and antibodies. Examples of
serological methods for detection of leishmanial antigens is ELISA and
for antibody detection ICT (Immunochromatographic test).
Molecular diagnosis: Polymerase chain reaction (PCR) to detect the
DNA of the parasite.
70. DIAGNOSIS
Leishmanin skin test (Montenegro test):
It is a delayed hypersensitivity test.
0.1 ml of killed promastigote suspension is injected intradermally on the
dorsoventral aspect of forearm.
Positive result is indicated by an induration and erythema of 5 mm or more
after 48–72 hours.
Positive result indicates prior exposure to leishmanial parasite.
71. DIAGNOSIS
Non-specific serum tests: These tests are based on the greatly
increased globulin content of serum in the disease.
(a) Napier’s aldehyde or formogel test - 1 ml of serum from the patient
is taken in a small test tube, a drop of formalin (40% formaldehyde) is
added, shaken, and kept in a rack at room temperature.
72. DIAGNOSIS
A control tube with normal serum is also set up. A positive reaction is
jellification and opacification of the test serum, resembling the
coagulated white of egg appearing within 3–30 minutes. About 85% of
patients with disease of 4 months or more give positive reaction.
73. DIAGNOSIS
(b) Chopra’s antimony test: It is done by taking 0.2 ml of serum diluted
1:10 with distilled water in a tube and overlaying with few drops of 4%
solution of urea stibamine. Formation of floculant precipitate indicates
positive test.
74. DIAGNOSIS
Full blood count: shows normocytic normochromic anemia and
thrombocytopenia.
Leucocyte count reveals leucopenia accompanied by a relative increase
of lymphocytes and monocytes.
Serum shows hypergammaglobulinemia and a reversal of the albumin:
globulin ratio.
75. TREATMENT
Treatment has been based on pentavalent antimonial compounds.
Following the increasing incidence of VL cases in immunocompromised
patients and the rise of acquired resistance to antimonials,
amphotericin B, mainly in its liposomal form, has joined the antimonials
as a first-line drug for Leishmaniasis.
76. TREATMENT
Two pentavalent antimonial preparations are available:
Sodium stibogluconate
Meglumine antimonate
Dosage: The daily dose is 20 mg/kg by rapid intravenous (IV) infusion or
intramuscular (IM) injection for 20–30 days.
77. PREVENTION/CONTROL
Wearing clothes that cover as much skin as possible and using bed nets.
Sandflies are sensitive to various repellents used against mosquitoes.
Use of insecticides
Treatment of cases
78. CONCLUSION
In conclusion, during this lecture we have been able to classify
Leishmaniasis, identify the aetiological agents for the various clinical
syndromes, outline pathogenesis, clinical features, diagnosis and
treatment modalities of Leishmaniasis.
79. REFERENCES
Mandell, Douglas and Bennett’s Principles and Practice of infectious
Diseases 7th Edition.
Medical Parasitology 2nd Edition by Arora
Manson’s Tropical Diseases
