Leishmania spp.

) )leishmaniasis
Cutaneous form (Oriental sore):
 L. tropica, L. major, L. mexicana,
 
Mucocutaneous form
 L. braziliensis

Visceral form (Kala azar):
 L. donovani (India)
L.Infantum (Mediterranean form of kala azar )
 Leshmaniasis
geographic distribution

2 million new cases/ year (2/3 CL; 1/3 VL)
Insect vector:
SAND FLY

Old World
Phlebotomus sp.
Sergentomya sp.

New World
Lutzomyia sp.
Brumptomya sp.
sandfly
 Leishmania
morphology

 Promastigote
)leptomonad) seen in
sand fly

 Amastigote )leishmania)
seen in the mammalian
host )LD body leishman-
amastigote Donovan body)
 Kinetoplast

The maxicircles contain the rRNA and structural genes like 
cytochrome oxidase subunits I, II, and III, cytochrome b,  
amastigote
Promastigotes of Leishmania sp. 
The promastigotes are approximately 25 µm in length.
A macrophage filled with Leishmania amastigotes.
 Old World Cutaneous
Leishmaniasis

Self-healing skin lesions

L. Major and L.tropica 

causes a moist, cutaneous,
ulcerlike lesion at the site of the
bite;
it starts as a papule that runs
an acute course )1-3 weeks).

Natural healing of the infection

)2-12 months)
• Transmission via the sand fly:
• Reservoirs )gerbil, rodents, dogs) to human
• Human to human.

• Direct transmission Human-Human

---Primitive form of vaccination
 • New World Cutaneous Leishmaniasis

• Rural diseases that are more prevalent among males who work in
the forests

•  L. mexicana . The ulcer usually heals spontaneously in a few

months.
• When the bite occurs on the ear it results in chronic lesions known
as chiclero's ulcer.
• Because the cartilage of the ear pinna is poorly vascularized the
immune response is weak, and in 40% of cases the result is
mutilation of the pinna.
• Found principally in Central America and Mexico where it occurs in
the forest dwelling people who harvest latex from the chicle trees to
be used in the manufacture of chewing gum.
 Cutaneous Leishmaniasis
Diagnosis
• Diagnosis is made by
using scrapings from
the edge of the ulcer
smeared on a slide
and stained and
examined
microscopically for
amastigotes.
• Diagnosis
• Recently PCR amplification of parasite genes has been used for diagnosis.
Tissue biopsies are touched to filters and the filters are hybridized with
labeled probes against parasite genes.

• Treatment
• Pentavalent antimonials may be used: i.e. Stilbophen )first used in 1912),
or Pentostam )first used in 1947), or Glucantime )first used in 1950), but
ordinarily such treatments are not necessary.
• Local antibiotic to avoid secondary infection

•  Control
• 1. Cover sores
• 2. Remove reservoirs
• 3. Remove vectors near habitation using insecticides
• 4. Screen against sandflies and use repellents
 • MUCOCUTANEOUS LEISHMANIASIS 
)occurs only in the New World)

• Beginning like cutaneous leishmaniasis and the ulcer usually heals

spontaneously within 6-15 months. However, there is metastatic
spread of the promastigotes from the site of the bite via the
lymphatics.

• L. braziliensis:
• Metastatic lesion involves the nasal and buccal mucosa causing
destruction and malformations of the cartilage and soft tissues.
• Death may occur from secondary infections or respiratory
complications.

• Reservoir: sloths and anteaters

• Diagnosis: Like cuteaneous leishmaniasis

• Treatment:Treatment is usually ineffective despite intramuscular or

intravenous injections of pentavalent antimonials. Secondary
bacterial infections are treated with antibiotics.
• Liposomal amphotericin B 3mg/kg. )ISP meeting 2006) 
Mucocutaneous
leishmaniasis
sloths
 • VISCERAL LEISHMANIASIS (Kala Azar)

• L. donovani is the classic type found in India.

• This is a metastatic disease.

• Rarely is a lesion seen at the site of bite and parasites

are only occasionally seen in blood, but are present in
the spleen and lymph nodes.

• The incubation period is 1-4 months.

• Disease is characterized by fever, anemia,

splenomegaly, wasting, imbalance of serum proteins
)A/G ratio is reversed) and hyperpigmentation of the
skin. The death rate is very high if left untreated.

• Reservoir: none
 Visceral Leishmania

months: fever chills, 1-4 

diarrhea, dysentery
Progressive hepato- 
splenomegaly
skin hyperpigmentation 
Death, if untreated 
• L. infantum
• Mediterranean form of kala azar

• Dogs, jackals and foxes as reservoirs.

• Humans are accidental hosts.

• Principally occurs in children, but no one knows why.

• Vector: P. araiasi and P. major.

Dog infected with L. infantum
Am J Trop Med Hyg. 1998 Nov;59)5):722-5.

• Emergence of visceral leishmaniasis in 
central Israel.
Baneth G, Dank G, Keren-Kornblatt E, Sekeles E, Adini I, 
Eisenberger CL, Schnur LF, King R, Jaffe CL.
 Visceral Leishmaniasis treatment
• Sodium stibogluconate or Pentastam, a derivative of antimony

Severe reactions including death occur in 10% of those treated.

It is very expensive, and the recommended one month treatment costs around
$150.

Drug resistance has also developed. Up to 70% of infected patients in India are
resistant to this drug.

Pentamidine isothionate has been used in antimony-resistant visceral

leishmaniasis, but although the initial response is often good, the relapse
rate is high and it is associated with serious side-effects.

• Recently a new drug was developed, miltefosine (Impavido®). This is a 
membrane signaling pathway inhibitor. 
• This can be taken orally and is very effective against visceral 
leishmaniasis. In clinical trials has a 95% cure rate!  
• Miltefosine was originally developed for breast cancer but was found 
in a screen to be active against Leishmania parasites by Simon Croft 
in 1987. It has recently been approved for use in India.
 Virulence factors inLeishmania
Life inside a macrophage
1- Resistance to superoxide anion )oxydative burst):

Hydroperoxide+ Reduced gluthatione

ROOH + 2GSH  ROH + 2GSSG + H20
)Lipophosphoglycan )LPG
In the insect vector:
2. LPG inhibits the release of midgut proteases in the fly 

4. LPG mediates the attachment of promastigotes to the gut 
wall 

In the mammalian host:
• A direct measurement of oxidative burst in stimulated 
macrophages showed that LPG inhibited this activity. 

• LPG inhibits the induction of the burst.

Glycosylphosphatidylinositol
)GPI)-anchored
 gp63

Major surface glycoprotein of L. major

promastigotes
It is a GPI-anchored zinc metalloprotease
of 63 kD.
The gp63 protein appears to mimic
fibronectin
The gp63 protein can also degrade
lysosomal enzymes
The A2 gene in L. donovani and L. major

•The A2 gene family was first identified in L. donovani,

which is specific to the amastigote stage.
•L. major does contain A2 genes, but they are not
expressed and lack the multiple repeats in the protein
coding regions = pseudogenes.
•A2 genes are tanden repeated with a distinct gene family
termed the A2erl genes. A2rel is expressed at equal levels
in the promastigote and amastigote.
•L. donovani amastigotes deficient in A2 protein )asRNA,
gene k.o.) are attenuated with respect to survival in visceral
organs of infected mice.
•L. major genetically engineered to express A2 produced
higher infection levels in the spleen and liver, compared to
control L. major.