Unveiling the Intricacies of Leishmania donovani: Structure, Life Cycle, Pathogenicity, Diagnosis, Treatment, and Clinical Presentation

Habitat of Leishmania Donovani:
• Leishmania donovani like Trypanosoma is a haeomoflagellate parasite.
In man it resides in Leishmanial form in lymphoid—macrophage
(Reticuloendothelial) cells of the spleen, liver, bone- marrow, intestine
and lymph glands.
• In its vector host Sand fly, Phlebotomous it is found in Leptomonad form
in the intestine. The disease caused by leishmania is known as
Leishmaniasis or Kala-azar. The disease is prevalent in the Eastern
hemisphere specially in India, Southern U.S.S.R., Burma, Central China,
Iraq etc.

Morphology
• In man the intracellular parasite occurs as
Leishmanial forms. These are oval or spherical in
shape and measure 2-4 micra by 1·5-2 micra. The
flagallum is absent. Nucleus and kenetoplast are
well formed. The kinetoplast is elongated and lie
perpendicular or tangential to the nucleus.
• An axoneme ranging between the kinetoplast and
periplast may remain present. In the intermediate
host the parasite occurs as Leptomonad forms. The
leptomonad forms are long, slender measuring 7-
20 micron. It has a long flagellum.

The parasite exists in two forms:
• The amastigote form in man and other mammals, and the promastigote
form in the sand-fly.
Amastigote form:
• The amastigote form of Leishmania Donovani is also called Leishman-
Donovan bodies. It is an ovoid or rounded cell, about 2.4 µm-3.5 µm
wide. It is typically intracellular, being found within the cells of
reticuloendothelial system (RE system) like macrophages in the spleen,
monocytes, neutrophils, liver and bone marrow, and less often in other
locations such as intestinal mucosa and mesenteric lymph nodes.
• Smears stained with Leishman, Giemsa or Wright stains show a pale blue
cytoplasm enclosed by a limiting membrane.

Promastigote form:
• The promastigote form of Leishmania Donovani is found in the midgut
(stomach) of sand-fly. Initially it is short oval or pear-shaped forms
which subsequently become long spindle-shaped cells, 15-25 µm long,
carrying a single flagellum of 15-30 µm long.
• Stained films show pale blue cytoplasm, with a red nucleus in the centre.
The kinetoplast lies transversely near the anterior end. Near the root of
the flagellum is present a vacuole.
• As the flagellum extends anteriorly without carrying
back on the body, there is no undulating membrane.

Life-Cycle of Leishmania Donovani:
• All leishmania pass their life cycle in two hosts. In man and some other
mammals (definitive host) they occur exclusively in the amastigote form,
having an ovoid body containing a nucleus and kinetoplast. In the sand-
fly (intermediate host), they occur in promastigote form, with a spindle-
shaped body and a single flagellum arising from the anterior end.
Definitive host:
• In the body of definitive host, Leishmanias are mostly found within
macrophages, monocytes, neutrophils or endothelial cells. Within these
cells they multiply by binary fission, producing numerous daughter cells
that distend the cells and rupture them.

• The liberated daughter cells, in turn are phagocytosed by other
macrophages and histiocytes, which are also killed by the parasites. By
this way, the parasites eventually severely damage the reticuloendothelial
(RE) system, a system that plays a critical role in the host defense.
• Interestingly, amastigotes of Leishmania Donovani engulfed by
neutrophils and eosinophils are killed, but in untreated cases these
polymorphonuclear leucocytes have little or no effects in the eventual
outcome of the disease. Due to damage of RE system, small numbers of
amastigotes can be found in peripheral blood, but rarely they may be
seen in faeces, urine and nasal secretions.

• Intermediate host:
• When a vector sand-fly feeds on an infected person, the amastigotes present
in peripheral blood and tissue fluids enter the insect along with its blood
meal. In the midgut (stomach) of the sand-fly, the amastigotes elongate and
develop into the promastigote form.
• The promastigotes multiply by longitudinal binary fission and reach
enormous numbers. They may be seen as large rosettes, with their flagella
entangled. By fourth or fifth day after feeding the parasites move forward to
oesophagus and pharynx, where they accumulate and block the passage.
• Such “blocked fleas” have difficulty in sucking blood when they bite a
person (host) and attempt to suck blood, plugs of adherent parasites may get
dislodged from the pharynx and deposited in the punctured wound. The
promastigotes so deposited are phagocytosed by macrophages inside which
they change into amastigotes and start multiplying.

• These, in turn, enter the midgut of sand-fly when it bites the infected
person. It takes about 6-10 days for the promastigotes to reach adequate
numbers so as to block the buccal cavity and pharynx of the sand-fly.
This is, therefore, the duration of the extrinsic incubation period.

Pathogenicity of Leishmania Donovani:
• Mode of transmission and incubation period – The infection is
transmitted by the bite of the vector sand-fly Phlebotomus argentipes.
The disease is not zoonotic in India, man being the only host and
reservoir.
• The incubation period is usually 3 to 6 months, though occasionally it
may be as short as 10 days or as long as two years. Cutaneous lesion at
the site of bite of the sand-fly is not seen in Indian patients but is
common in patients in Sudan and Middle East.

Pathogenesis:
• The disease caused by Leishmania Donovani was first characterised in
India, and it is known as Kala azar (meaning black sickness), Dum Dum
fever, Burdwan fever or Tropical splenomegaly. The onset of the visceral
leishmaniasis is typically insidious. The clinical illness begins with fever,
which may be continuous, remittent or irregular.
• Splenomegaly starts early and is progressive and massive. About 10-20%
patients who recovered from kala azar may develop post kala azar dermal
leishmaniasis (PKDL). The dermal lesions usually develop about a year
or two after recovery from the systemic disease.
• Kala azar is a reticuloendotheliosis resulting from the invasion of the
reticuloendothelial system by L. donovani. Several organs are affected
resulting various symptoms.

(i) Splenomegaly:
• The spleen is the organ most affected. It is grossly enlarged and the
capsule is frequently thickened due to perisplenitis. The amastigotes
multiply enormously in the fixed macrophages to produce a blockade of
the RE system.
• So blood-forming organs like spleen undergoes compensatory production
of macrophages and other phagocytes to the detriment of red cell
production. Thus, the spleen become greatly enlarged while the patient
becomes generally anaemic and emaciated.

(ii) Hepatomegaly:
• The liver is enlarged, the Kuffer cells and vascular endothelial cells are heavily
parasitized, but hepatocytes are not affected. Liver function is therefore not
seriously affected, though prothrombin production is commonly decreased. The
sinusoidal capillaries are dilated and engorged. Some degree of fatty degeneration
is seen.
• The bone marrow is heavily infiltrated with parasitized macrophages which may
crowd out the haemopoietic tissues. Peripheral lymph nodes and lymphoid tissues
of the nasopharynx and intestine are hypertrophic due to infiltration with
parasitized cells. The disease progresses for several months, with periods of
apyrexia followed again by fever.
• The skin becomes dry, rough and darkly pigmented. The hair becomes thin and
brittle. Epistaxis and bleeding gums are common. Most untreated patients die in
about two years due to some inter-current disease like dysentery and invasion of
secondary pathogens that the body is unable to combat.

Classification of different kinds of kala-azar:
i. Indian kala-azar:
• Dumdum fever, the classical form of L. donovani. It occurs in India, affecting
young adults, 60 percent of infection being in the age group 10-20 years. The
infection is transmitted by sand-fly, Phlebotomus argentipes.
ii. Chinese kala-azar:
• Chiefly occurs in northern China, mainly a condition of children with dog as a
reservoir. Transmitted by P. chinensis and P. sergenti.
iii. Mediterranean kala-azar:
• Chiefly occurs in the Mediterranean area, Southern Europe and parts of tropical
Africa. 80 per cent of cases found in children under 5 years of age and 94 per
cent in those under 10 years. Dog serves as a reservoir host and in this animal
infection rates may be as high as or higher than, in the human population. The
infection is transmitted by P. major, and P. perniciosus.

iv. African kala-azar:
• Chiefly prevalents in Kenya and Sudan; 66 percent of cases occur in
young adults. Natural infections have been found in a Cercopithecus mon-
key, a gerbil and a ground squirrel. This is characterised by the early skin
lesion and the infection is transmitted by P. orientalis and P. martini.
v. Russian kala-azar:
• This is an infection with a zoonotic reservoir in dogs and jackals in the
Caucasus, Turkistan and other Republics of U.S.S.R. Transmitted by P.
arkaplensis.
vi. American kala-azar:
• Occurs from Mexico to Southern Argentina and in U.SA. This disease
occurs in humans and the fox serves as reservoir host. The transmitting
flies are P. intermedins and P. longipalus.

Symptoms:
• The incubation period of kala-azar is long and generally varies from 3-6 months
and symptoms may appear even after 2 years.
• Pyrexia is often an early symptom and it may be continuous or remittent in type,
becoming intermittent at a later stage.
• Splenic enlargement is one of the most striking features and the organ progres-
sively enlarges.
• The liver is also enlarged but not as much as the spleen.
• Irregular fever is also observed.
• In a fully developed case of kala-azar emaciation, anaemia due to reduction in
number of blood cells become noticeable.
• The skin over the entire body is dry, rough and harsh and is often pigmented
(darkened).
• The hair becomes brittle and falls out.

Treatment and Prevention of Disease Caused by Leishmania Donovani:
• The standard treatment is the pentavalent antimonial sodium
stibogluconate given I.V. (intravenous), 600 mg daily for 6 days. An
alternative is pentamidine 4 mg/kg/day given I.M. (intra muscular) for 10
days. In refractory cases, splenectomy followed by chemotherapy may
succeed.
Prevention:
• Prophylactic measures consist of treating all cases, eradication of the
vector sand-fly and personal prophylaxis by using anti-sand-fly
measures.

Unveiling the Intricacies of Leishmania donovani: Structure, Life Cycle, Pathogenicity, Diagnosis, Treatment, and Clinical Presentation

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Unveiling the Intricacies of Leishmania donovani: Structure, Life Cycle, Pathogenicity, Diagnosis, Treatment, and Clinical Presentation