Leishmaniasis

DR VARADHARAJ M
Definition
Leishmaniasis is a complex group of disorder primarily affects the hosts
reticuloendothelial system.
Leishmaniasis is caused by unicellular eukaryotic obligatory intracellular protozoa
of genus leishmania in the order kinetoplastida and family trypanosomatidae.
Geographical Distribution: Transmitted by phlebotomine sandflies of genus
phlebotomus in regions of Africa,the Mediterranean, southern europe (old world)
and the genus Lutzomyia in south and central America (New world)
In India,Nepal,Bangladesh and Sudan 90% cases of Visceral leishmaniasis are
reported
PATHOGENESIS
● Leishmania organism occurs in two forms : extracellular ,flagellate
promastigote in sandfly vector , intracellular ,non-flagellate amastigotes in
humans
● Promastigotes are introduced through probiscus of female sandfly into skin of
host
● Neutrophills predominate among the host cells and take up promastigote at the
site of parasite delivery
● Infected neutrophils may undergo apoptosis and release viable parasites that
are taken up by macrophages or apoptotic cells may themselves be taken up
by macrophages and dendritic cells
● Parasites multiply as amastigotes inside macrophages causing cell rupture with
subsequent invasion of other macrophages
● While feeding , sandflies pickup amastigotes which transforms to promastigote
in flies posterior midgut then migrates to anterior midgut and can infect a new
host when flies take another blood meal
VISCERAL LEISHMANIASIS

● Visceral leishmaniasis known as kala-azar meaning black fever is caused by

leishmania donovani complex including Leishmania donovani and Leishmania
infantum
● In endemics ,the disease is more chronic with young adults and children.,in
epidemics all age groups are susceptible,and the disease is often acute
● India ,Bangladesh,Sudan,Ethopia and Brazil are the four largest foci of
visceral leishmania and accounts for 90% of world’s burden
● In Mediterranean Europe an established endemic disease due to Leishmania
infantum accounts for 70% of adult visceral leishmania cases associated with
HIV co-infection
Clinical features of Visceral leishmania
● Visce leishmania usually presents as an abrupt onset of moderate to high
grade fever associated with chills and rigor
● Anemia appears early and may become severe enough to cause
congestive heart failure
● Spleen may be palpable by second week of illness and depending upon
duration of illness may beccome hugely enlarged
● Lymphadenopathy is common in most endemic region
● Skin gradually develops dark discolouration due to hyperpigmentation
● In advanced illness hypoalbuminemia manifest as padal edema and
ascites
● Secondary infections such as measles,pnemonia,tuberculosis,herpes
zoster,chickenpox,scabies may also occur
● Untreated disease is fatal in most patients,including 100% of those with
HIV co-infection
Laboratory Diagnosis of Kala-azar
DIRECT EVIDENCES :
SPECIMEN:
● Aspirates from bone marrow,spleen,lymph node,blood
SMEAR AND STAINING(LEISHMAN OR GIEMSA)
● Amastigote form in monocytes
CULTURE IN NNN MEDIA
● Incubation at 22 degree celsius
● Incubation time 1-2 weeks
● Findings:Promastigote form of parasites
INDIRECT EVIDENCES:
SEROLOGY:
For detection of antigen:
● ELISA
● RIA(RadioImmunoAssay)
For detection of antibody:
● IFAT(Indirect Immuno Fluorescent Antibody Test)
● DAT(Direct Agglutination Test)
● ICT(Indirect Chromatographic Test)
● CFT(Complement Fixation Test)
● Rk39
NON SPECIFIC TEST:
● Aldehyde test
● Antimony test
BLOOD COUNT:
● Anemia and leucopenia(neutropenia) with lymphocytosis and monocytosis
MOLECULAR DIAGNOSIS:
● PCR(Polymerase Chain Reaction)
TREATMENT OF VISCERAL LEISHMANIA
PENTAVALENT ANTIMONIAL COMPOUNDS
● Two pentavalent antimonial preparations available : sodium stibogluconate
and meglumine antimonate
● Daily dose is 20mg/kg by IV infusion or IM injection,therapy continues for 28-
30 days
● Complications:
● Prolongation of ST segment >0.5 s may lead to ventricular arrhythmia and
sudden death
● Chemical pancreatitis is common but usually doesn’t require discontinuation
of treatment
Amphotericin B
● Amphotericin B available in two formulations:AmpB deoxycholate and
liposomal AmpB
● AmpB deoxycholate administered in doses of 0.75 -1.0 mg/kg on alternate
days for a total of 15 infusions
● Complications: Fever with chills ,nausea ,vomiting,thrombophlebitis in infused
veins , renal dysfunction,hypokalemia,rarely ellicits bine marrow
suppression,myocarditis which can be fatal
● Liposomal AmpB,preferentially taken up by reticuloendothelial tissues,dose of
3mg/kg daily on days 1-5,14,21
Paromomycin
● Dose:11mg of base/kg daily for 21 days through IM route
COMPLICATIONS: Hepatotoxicity,reversible ototoxicity,tetany
MILTEFOSINE
● Therapeutic regimen of daily dose 50 mg for 28 days for patients weighing <25kg,
twice-daily dose of 50 mg for 28 days for paternity weighing >25kg and 2.5mg/kgfor
28 days for children 2-11 years of age
Complications: contraindicated in pregnancy
In IMMUNOCOMPROMISED HOST
● LiposomalAmpB is the drug of choice for HIV/Vl coinfection both for primary case
and for relapse ,total dose of 40mg/kg,administered ad 4mg/kg on days 1-
5,10,17,24,31 and 38 is considered optimal
MULTIDRUG THERAPY
● One dose of liposomalAmpB followed by miltefosine for 7 days , paromomycin
for 10 days or both miltefosine and paromomycin simultaneously for 10 days
produced a cure rate of>97%
ADVANTAGES :
● Better compliance and lower cost
● Less toxicity due to lower drug dose and short duration of treatment
● Reduced likelihood to develop resistance
POST KALA AZAR DERMAL LEISHMANIASIS
● Post kala azar dermal leishmaniasis is so called because it developes after
kala azar is cured
● Also called dermal leishmanoid
PREVALENCE
● In endemic areas of Indian subcontinent mostly in west bengal and
Bangladesh and occasionally in East Africa
● PKDL affects about 20% of patients in India
● Hypopigmented and raised erythematous patches can be found on face,trunk
of body,and limbs.Occasionally there is ulceration of lips ,tongue.Amastigotes
can be demonstrated in papules and nodules
POST KALA AZAR DERMAL LEISHMANIASIS
CUTANEOUS LEISHMANIASIS
Old world cutaneous leishmaniasis
● Leishmania tropica:Infection is often referred to as dry urban oriental
sore .Dry painless ulcers 25-70mm in diameter which are usually self-healing
usually after 1-2years but often leave disfiguring scars.It can last many years
and is difficult to treat.
Leishmania Major

● Infection is often referred to as wet oriental sore.The early papule is often

inflamed and resembles a boil of 5-10mm in diameter which rapidly develops
into a large uneven ulcer which is self healing,multiple lesions may occur in
non-immune persons
NEW WORLD CUTANEOUS LEISHMANIA
LEISHMANIA MEXICANA:Causes chiclero ulcer or bay sore.Lesions of the body
tends to be self-healing but those on ear may destroy pinna of ear
LEISHMANIA PANAMENSIS:Causes single or few skin ulcers which are not self
healing.Lymphatic involvement is common resulting in secondary nodules
Cutaneous leishmaniasis
Treatment of cutaneous leishmaniasis:
● Pentavalent antimonial is the first-line drug dose of 20mg/kg for 20 days
● For Leishmania guyanensis pentamidine isethionate is the drug of choice-2
injections of 4mg/kg of 48hrs interval
● Leishmania aethiopica responds to parmomycin 16mg/kg but not to
antimonials
● Leishmania major Miltefosine has been used in doses of 2.5mg/kg for 28 days
● Relapses usually respond to second course of treatment
● A trial of oral flucanazole to leishmania major resulted in a higher rate of cure
than placebo
DIFFUSE CUTANEOUS LEISHMANIASIS

LEISHMANIA AETHIOPICA :
● A cutaneous lesion is produced that is similar to typical oriental
sore with healing in 1-3 years.Leishmania aethiopica can cause
diffuse cutaneous leishmaniasis in patients with litt or no cell
mediated immunity against the parasite.This is an incurable
condition characterized by the formation of disfiguring nodules
over the surface of the body.Amastigotes can be demonstrated
in the nodules
MUCOCUTANEOUS LEISHMANIASIS
Treatment of mucosal leishmaniasis
● The regimen of choice is a pentavalent antimonial agent
administered at a dose of 20mg/kg for 30 days
● AmpB deoxycholate total dose of 25-45 mg/kg ,2-3mg/kg for 20days
is considered adequate
● Miltefosine 2.5mg/kg for 28days cured 71% of cases
● Patients require long term treatment with repeated oropharyngeal
and nasal examination
PREVENTION AND CONTROL OF LEISHMANIASIS

PERSONAL PROPHYLAXIS:
● Use of mosquito nets,periodic fumigation,insect repellants
● Early detection and treatment of infected persons,especially in areas
where humans ar the only or important reservoirs of infection
● Avoiding endemic areas especially at times when sandflies are most
active
● Use of insecticide impregnated bednets and curtains
● Vector control by use of ight traps,sticky paper traps or residual insectiside
spraying of houses and farm buildings
● Destruction of stray dogs and infected domestic dogs in areas where dogs are
the main reservoir hosts
● Elimination and contr of rodents in areas where these are sources of human
infections
● Two vaccines,Leishmune and Leish-Tec, are licenced in Brazil,Leishmune
provides significant protection to vaccinated dogs,Canileish and Letfend are
licenced canine vaccines approved for use in Europe
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