1. INTRODUCTION
► Leishmaniasis are a group of infections caused by
intracellular protozoan parasites belonging to the
genus Leishmania, family Trypanosomatidae, order
Kinetoplastida.
► Different names : Oriental sore, Aleppo evil,
Delhi boil, Baghdad sore, Rose of Jericho, Uta,
Espundia (mucocutaneous), kala-azar, Black
fever (visceral)
2. CLASSIFICATION
► Depending on the extent and severity of involvement,
infections in the human host can be classified as
➢ - Cutaneous leishmaniasis
▪ New world – L.braziliensis, L.mexicana
▪ Old world – L.major, L.tropica, L.aethiopica, L.infantum
➢ - Diffuse cutaneous leishmaniasis – L.mexicana,
L.aethiopica
➢ - Mucocutaneous leishmaniasis – L.braziliensis,
L.aethiopica
➢ - Visceral leishmaniasis – L.donovani, L.infantum
► Based on the location of enzymatically active proteins
(isoenzymes), leishmaniasis has been reclassified into
ZYMODEMES. Zymodemes are defined as group of
leishmania organisms that share same electrophoretic
migration pattern of isoenzyme
3. EPIDEMOLOGY
► VL:- Prevelant in all continents
except Australia & Antarctica.
► Affects 88 countries worldwide &
350 million people live in these
endangered zones
► Highest in central & South
America, Southern Europe, Central
Africa & parts of Southern &
central Asia.
► CL - 1.5-2 million new cases each
year
► 90% are in Afghanistan, Algeria,
Iran, Iraq, Saudi Arabia, Syria,
Brazil and Peru.
4. EPIDEMOLOGY
In India :
► VL- 90% cases in Bihar, followed by West Bengal & Eastern
UP.
► CL – PKDL- North Eastern India
► L. Tropica – Delhi, HP, Punjab, Haryana, Rajasthan
5. TRANSMISSION
► Bite of an infected Sand fly
► Rarely – 1. Tranfusion
2. Sexual intercourse
3. Placental transfer
4. Lab accident
PARASITE
► Obligate intracellular parasite
► Completes life cycle in two hosts and exists in three
morphologic types:
Amastogote – Non flagellate form, in macrophage / RE cells of
vertebrates.
Promastigote – flagellate form, in intestines of invertebrates
Paramastigote – Transitional stage between two invertebrates.
6. VECTOR : Sandflies
► Phlebotomine sandfiles of genus:
- Phlebotomus – Old world
- Lutzomyia and Psychopygu– New World
► Only females are hematophagus (blood sucking)
► More common in warm months.
► Pass through ordinary mesh screens and mosquito nets.
► Limited flight range – 250 mt.
RESERVOIR
► Rodents – Visceral
► Dogs – Cutaneous
► Others -rats , mice, cats, gerbits.
In India, man is the most common reservoir for cutaneous
leishmaniasis.
7. LIFE CYCLE OF LEISHMANIA
Amastigate form (Inf. Mammalian
tissue or blood)
Midgut of female
sandfly
Promastigate
multiplication
Migrate to
pharynx &
proboscis
Injected into new
mammalian host Enter dermis
Phagocytosed by
macrophages
Amastigate form
Multiplication
Disrupt macrophages
Release amastigotes
Enter new
macrophages
8. IMMUNOPATHOGENESIS
► Susceptibility to disease depends on the T-cell &
macrophage response
► Expansion of the Th1 subset with production of IL-2 & IFN-γ
leads to resolution of infection, while Th2 proliferation & IL-4
production leads to progression of the disease
► Factors that determine the type of response include
➢ Antigen presenting cells
➢ Antigenic load
➢ Type & amount of cytokines present at the time of
inoculation of parasites
➢ Specific leishmanial antigen
9. ADHESION & ESCAPE MECHANISMS OF
LEISHMANIA spp.
➢Binds lectin like binding sites on CD8+ cells
& mediates adhesion to macrophages
➢Inhibits insertion of C5b9 complex in
membrane, preventing lysis
➢Inhibits generation of respiratory bursts
through inhibition of protein kinase C
➢Inhibition of lysosomal β galactosidase
➢Oxygen radical scavenger
►Lipophosphogly
can
Mechanism of interaction with
host
Leishmania
10. ADHESION & ESCAPE MECHANISMS OF
LEISHMANIA spp.
➢Protease capable of degrading lysosomal
enzymes
➢Degradation of hydrogen peroxide
➢Inhibition of oxidative burst
►Glycoprotein 63
►Superoxide
dismutase
►Acid
phosphatase
Mechanism of interaction with
host
Leishmania
11. CLINICAL FEATURES
► Infection with Leishmania can either lead to clinically silent
disease or a spectrum of clinical signs depending on
➢ Immunological status of the individual
➢ Genetic background
➢ Nutritional status of the host
➢ Number of parasites and their virulence factors
➢ Site of inoculation
➢ Composition of sandfly saliva
12. Mucocutaneous form
➢Skin lesions- papules, ulcers &
nodules
➢Mucosal lesions present with
in 2 years of skin lesions in
50% of cases
➢ most common site is nose
where it starts as a nodule on
the inferior turbinate or
septum f/b pharynx,palate,
larynx & upper lip l/t
destruction of cartilage &
disfigurement – ESPUNDIA
➢Earlier seen in 80% cases but
now <5%
➢Lutzomya
longipalpis
➢Lu. umbratilis
➢Lu. spinicrassa
➢Lu. trapidoi
➢Lu. migonei
➢Phlebotomus
yucumensis
➢P.lianosmartinsi
•L.braziliensis
•complex
•L.braziliensis
braziliensis
•L.braziliensis
guyanensis
•L.braziliensis
panamensis
TYPE OF DISEASEVECTORAGENT
13. ➢Visceral involvement not
usually seen but death can
occur due to secondary
bacterial infection, pharyngeal
obstruction & malnutrition
TYPE OF DISEASEVECTORAGENT
14.
15.
16. ➢Mucocutaneous form
➢Small erythematous papules
occur at site of insect bite –
ulcerated nodule – heal
leaving behind a depressed
scar
➢Ears are involved in 40-55% of
cases
➢Cutaneous nodules are the
most common presentation in
Texas
➢May cause Diffuse cutaneous
leishmaniasis
➢Lutzomya
anthopora
➢Lutzomya
diabolica
➢Lutzomya
olmeca olmeca
►L.mexicana
complex
►L.mexicana
amazonensis
►L.mexicana
pifanoi
►L.mexicana
aristedesi
►L.mexicana
garnhami
►L.mexicana
venezuelensis
TYPE OF DISEASEVECTORAGENT
17.
18. ➢Two different forma are
recognized-
➢Cutaneous Andrean form – c/a
UTA
➢Amazonian jungle form – has
mucous membrane
involvement resembling
ESPUNDIA
➢Lutzomya
noguchii
➢Lutzomya
verrucarum
➢Lutzomya
peruensis
►L.peruviana
TYPE OF DISEASEVECTORAGENT
19.
20. Cutaneous form
➢c/as Oriental sore ( dry),
Aleppo button, Jericho boil,
Pendinnsk ulcer, Urban or
Anthroponotic leishmaniasis
➢Starts as a small brownish
nodule after an incubation
period of about 2 months
➢Increases in size to 1-2 cms
in diameter over 6 months
➢Ulcers & sores may develop
which heal by permanent
scarring in 8-12 months
➢P.perfiliewi
➢P.pappatasi
➢P.sergenti
➢P.longicuspis
L.tropica
TYPE OF DISEASEVECTORAGENT
21.
22. Cutaneous form
➢Wet form of oriental sore, also
c/as zoonotic or rural
leishmaniasis
➢Starts as a small papule which
appears immediately after
insect bite or after 2-4 weeks
➢Enlarges in size & becomes
crusted in center, which on
removal shows an ulcer
➢Heals with depressed scar after
6-12 months but may remain
active >24 months – NON
HEALING CHRONIC
CUTANEOUS LEISHMANIASIS
➢P.duboscqi
➢P.pappatasi
➢P.salehi
➢P.caucasicus
L.major
TYPE OF DISEASEVECTORAGENT
23. ➢Sub cutaneous nodules
develop along lymphatics
➢Lymph nodes are enlarged
➢No mucous membrane
involvement
TYPE OF DISEASEVECTORAGENT
24.
25.
26. Cutaneous form
➢Similar to L.major
➢In 20% cases, widespread
involvement that resembles
lepromatous leprosy
►L.aethiopica
TYPE OF DISEASEVECTORAGENT
27.
28. ➢Viscerocutaneous form
➢Causes MEDITERRANEAN or
INFANTILE KALA AZAR
➢90% of affected people are
children < 5 years
➢Cutaneous lesions are usually
more inflammatory & more
likely to be solitary than those
caused by L.major
➢P.anasi
➢P.longicuspis
➢P.major
➢P.orientalis
➢P.perniciosus
➢P.tobbi
➢P.martini
➢P.argentipis
➢P.chinensis
L.infantum
TYPE OF DISEASEVECTORAGENT
29. LEISHMANIASIS RECIDIVANS
► Also c/as recurrent leishmaniasis, Metaleishmaniasis,
Leishmaniasis recidiva cutis, lupoid leishmaniasis, Late
cutaneous leishmaniasis
► Refers to development of new lesions in the center or
periphery of a scar of healed lesion of leishmaniasis
► First reported by Berlin in cases of oriental sore
► Causative organism – L.tropica in middle east
L.braziliensis in South America
► Rare in the New World, with only 11 cases reported so far
► Recurrent disease is due to reactivation of dormant
organism, with period of dormancy ranging from 1-15 years
30. LEISHMANIASIS RECIDIVANS
► Leishmania strain in 50% of recurrent lesions are different
from the initial strain, suggesting
▪ Change in immune status of host
▪ An exogenous re-infection
► Presents clinically as scaly, erythematous papules with in
the scar of healed lesions
► sometimes ulcers, psoriasiform lesions or veruccous lesions
may be present
► Lesions tend to resist treatment & become chronic
31.
32. POST KALA AZAR LEISHMANIASIS
► PKDL is a complication of VL, seen in patients who
have recovered from VL & who are otherwise well
► Seen mainly in Sudan & India, where it follows VL in
50% & 5-10% of cases respectively
► Causative organism is L.donovani
► Important role in inter epidemic periods of VL,
acting as reservoir of infection
► Pathogenesis is immunologically mediated
➢ High conc. of serum IL-10 in VL patients predict
development of PKDL
➢ production of IFN-γ by PBMC after treatment of VL
coincides with appearance of PKDL lesions
33.
34. POST KALA AZAR LEISHMANIASIS
TYPE OF RASH
► In Sudan, most common in papular or nodular rash (
51%)
➢ Other presentstions include – maculopapular (23%)
micropapular- measles like
(17%)
macular (9%)
► In India, there are 3 main presentations –
➢ Erythema & induration on butterfly area of face which
shows photosensitivity
➢ Multiple symmetric hypopigmented macules which
may coalesce
➢ Combination of papules, nodules & plaques
35.
36. POST KALA AZAR LEISHMANIASIS
► Uncommon presentations include – Annular, Warty,
Papillomatous, Fibroid or Xanthomatous types
► Ulceration is not a feature of Indian or Sudanese PKDL
DISTRIBUTION
► In Sudanese PKDL, lesions typically appear around mouth &
spread to other parts of face, then to upper arms & chest
► Indian PKDL also shows predilection for face & less
frequently over trunk & arms
► After treatment, lesions around mouth remain longest & are
first to recur in case of relapse
► In severe cases, mucosal lesions may appear on lips & palate
► Exposure to uv rays may be important in pathogenesis
► Lesions may show koebnerization
37. POST KALA AZAR LEISHMANIASIS
CLINICAL GRADES OF SEVERITY
► GRADE 1 – scattered maculopapular or nodular rash over
face, with or without some lesions on extremities
► GRADE 2 – dense maculopapular or nodular rash over
face, extending to chest, back, upper arms & legs with
scattered lesions on forearms & legs
► GRADE 3 – maculopapular or nodular rash covering most
parts of body, including hands & feet; crusting, ulceration,
scaling, sloughing and mucosal involvement can occur
38. INVESTIGATIONS
I. Demonstration of parasite
► Direct smears – SSS- Giemsa /Wright’s or leishmanin stain.
► Tissue smears – from edge of lesion’s
► Skin Bx – from edge
► FNAC.
► Nasal mucosal scrapings –MCL.
II. Culture
► Promastigste form is seen
► Various culture media include
▪ Novy, Mcneal Nicole (NNN) media
▪ Schneider’s culture medium.
▪ Rabbit blood agar.
39.
40. III. Animal Inoculation
► When parasite load in tissues is low
► Biopsy or aspirate specimens may be inoculated into
➢ Mouse foot pad – L. tropica
L. mexicana
➢ Hamster’s foot pad – other species
IV.Leishmanin skin test (Montenegro test)
► I/D test – Non-endemic areas – diagnostic
Endemic areas – survey work.
► 0.1 to 0.2 ml of antigen – 5 x 106
promastigote in 1
ml of 0.5% phenolized saline. Each 0.1 ml = 1 million
organisms.
INVESTIGATIONS
41. ► Evokes delayed type of hypersensitivity response.
► Read after 48-72 hours
► Induration > 5mm is positive
Grade I : 5-6 mm induration
Grade II : 7-8 mm induration
Grade III : > 8 mm induration
Grade IV : Blisters
► Negative in VL, DCL and Indian PKDL
► Positive in 90-98% patients of CL, MCL and African PKDL
► Cannot distinguish between active & quiescent disease
► False +VE – Glandular tuberculosis
Lepromatous leprosy
INVESTIGATIONS
45. VI.Polymerase Chain reaction
► PCR Assay can detect parasite DNA or RNA a few
weeks ahead of appearance of clinical signs and
symptoms.
► PCR assay has also been used for post therapeutic
follow up and for detection of relapse among HIV
infected patients.
► A PCR-ELISA technique developed recently is
reported to be sufficiently sensitive and specific for
diagnosis of MCL.
► PCR was found to be 100% specific and sensitive
method
JAAD 2003
INVESTIGATIONS
46. INVESTIGATIONS
VII. Serology
► More helpful in VL.
► Unreliable in CL – Sensitively ~ 70%
Specificity – low
1. Indirect immunofluorescent antibody test
(IFAT) – High specificity and sensitivity
2. ELISA – High sensitivity modification of this method
– dot – ELISA is a simpler immunoassay.
3. Western blot – sensitive
4. Direct agglutination test (DAT) – specificity
similar to IFAT but low sensitivity.
47. INVESTIGATIONS
5. Indirect immunoperoxidase assay (IPA)
More sensitive and specific than IFAT
6. Immunochromatographic ( rk39) test – sensitivity &
specificity of strip test are 82.4% & 100% resp. compared
to 100% & 92.7% for IFAT test
► For cutaneous leishmamasis – diagnosis rests on finding
parasite in the stains
► PCR is useful for confirming the diagnosis.
► IFAT – diagnosis in early stages.
48. TREATMENT OF CUTANEOUS
LEISHMANIASIS
► CL heals spontaneously in 6 months – 1 yr without
treatment, so expectant approach may be appropriate
particularly in endemic area.
► Patients requiring active treatment are :
▪ Lesions on cosmetically or functionally important sites
such as face or hands
▪ Associated lymphangitis
▪ Multiple or persistant lesions
▪ L. braziliensis/ panamensio –change into MCL.
▪ Lesions are large or overlie a joint.
Patients with MCL, DCL, PKDL do not heal without
treatment and require adequate systemic therapy
49. TREATMENT
Pentavalent antimony
► Antimony was first used in treatment of leishmaniasis
in 1912 & in its current formulation since 1945
► Only agent with clearly favourable therapeutic index
► Both trivalent and pentavalent compounds tried –
pentavalent is less cardiotoxic.
► Route – I/M or I/V
▪ I/M is preferred – ease of administration
Less toxic effects.
• Oral and rectal route – often not tolerated by
patients.
50. TREATMENT
► Preparations
▪ Sodium stibugluconate – pentostam (UK)
[100mg/ml] sodium antimony gluconate - India
(SAG)
▪ Meglumine antimonate – (85 mg/ml] Glucantime.
▪ These two drugs are equivalent in terms of
efficacy and toxicity.
► Dose : 20 mg/kg/day
► To minimize phlebitis – given as an I/V infusion in
150 ml of 5% dextrose over 2 hours.
51. TREATMENT
Duration of treatment
► CL – 20 days
► VL – 28 days
► Early MCL – 28 days
► PKDL – at least 4 months
Patient should be examined for clinical response 6
weeks after completing therapy and for 1 year for
overt sign of relapse
Mode of Action
1. Inhibition of synthesis of proteins, RNA and DNA –
Interfering with phosphorylation of ATP and GTP
which interferes with glycolysis and fatty acid
oxidation.
2. Anti-inflammatory effect
52. TREATMENT
ADVERSE EFFECTS
► Well tolerated , both in children and adults
► Common side effects include - Nausea, headache,
lethargy, myalgia, arthralgia.
► Pain at injection site
► Chemical pancreatitis (increase lipase/amylase)
53. TREATMENT
► Cardio toxicity : monitered by ECG changes
▪ Decrease T wave amplitude
▪ T-wave inversion
▪ Concave ST segment
▪ QT prolongation
► T/T should be interrupted if :
▪ QT > 0.5 secs.
▪ Significant arrhythmias
▪ 5 fold elevation of LFT
▪ Concave ST
► Can be resumed cautiously after 1-2 days to avoid
resistance
► Recurrent episodes of toxicity – switch to alternate drug.
54. TREATMENT
► Transient increase in liver enzymes
► Can be given safely in pregnancy
Monitoring
► HMG, S. biochem., ECG, Amylase –twice a week
Resistance
1. Primary resistance – Bihar (>30% pts. Of VL)
2. Secondary resistance – due to inadequate doses
and/or duration of treatment
55. ► Intralesional treatment
- For solitary uncomplicated CL lesions antimonials can
be injected intralesionally.
- Undiluted solution is infiltrated into the base and
edges of the ulcer or nodule so that blanching occurs.
- Injections are repeated every 2-3 days for 2-3 weeks.
TREATMENT
56. TREATMENT
Amphotericin B.
► TOC in antimony resistant patients.
► Polyene antibiotic from Streptomyces nodosus.
► Route – slow i/v with 5% dextaose.
Mechanism of action :
1. Interference with permeability of cell membrane.
2. Immuno modulatory effects.
Dose
► intital test dose – 1 mg
► usual daily dose ; started with 250 µg / kg/ day –
gradually increased to 1mg/kg/day infused over 2-4
hours.
57. TREATMENT
Adverse effects
➢ Hypersensitivity reactions – fever, rigors, hypotension,
nausea, vomiting, tinitus, bronchospasm, anaphylactoid
reaction.
➢ Phelbitis at site of injection
➢ Nephrotoxicity : in almost 100% patients
▪ Both glomerular and tubular damage
▪ RTA
▪ Incresed excretion of K & Mg l/t hypokalemia
& hypomagnesiumia
▪ Nephrocalcinosis
.
➢ Reversible normocytic normochromic anaemia
➢ Visual disturbances
➢ Ventricular arrhythmias – sudden cardiac arrest – with high
dose or rapid infusion
58. TREATMENT
LIPID – associated Amphotericin B
► Three formulations are available
i) Liposomal (Am Bisome)
ii) Colloidal dispersion (ABCD)
iii) Lipid complex (ABLC)
► Advantages
➢ Rapidly effective
➢ Taken up by macrophages and reaches high
concentration at infection site
➢ Less s/e - no nephrotoxicity
- no local toxicity
➢ Can be used at higher doses – 3-4 mg/kg
► Disadvantages : More expensive
59. TREATMENT
Physical Modalities
► Local heat : attractive, non toxic, inexpensive &
simple treatment option
• infrared radiation used to raise the skin temperature
to 55 C for 5 min
► L. braziliensis and L. mexicana are particularly heat
sensitive.
► Mechanism of action
Inhibition of amastigote replication
90% cure rate with single treatment with infra-red
radiation
99% cure rate with two treatments.
60. TREATMENT
► Cryotherapy : Useful for small lesions (<1 cm diameter)
▪ 30-90 sec cryoapplications performed with CO2 cryosurgical
machine with 1 cm cryoprobe tip, include the skin 2 mm
outside the lesions
▪ Complete response reported with average of 2 treatments.
▪ A large controlled study in Saudi Arabia showed the success
rate to be <30% with NO cryomachine
▪ Combination of cryotherapy & I/L stibugluconate superior
to either alone
► Other physical modalities used are
➢ CO2
laser
➢ curretage
➢ electrodessication
➢ surgical excision
61. TREATMENT
TRADITIONAL ANTI-INFECTIVE AGENTS
► Dapsone : 200 mg/day for 45 days cure rate – 82%
(Dogra et al)
➢ Exact mechanism not known, thought to decrease
phospholipid synthesis and /or interfere with folic acid
synthesis.
► Rifampin : 600-1200 mg/day (0-80% cure rate)
► Metronidazole : 250 mg tds for 10 days,3 cycles with 10
days rest (Pederson et al)
➢ 78% recovery rate with 250 mg bd for 15 days in
L.mexicana infection ( Beltran et al,1967 )
➢ subsequent studies – no clinical improvement.
62. TREATMENT
► Cotrimoxazole : 160/ 800 mg BD for 4 weeks
➢ 33 of 36 pts. showed resolution in 3-14 weeks
(Kandil, 1973)
➢ Efficacy similar to placebo in subsequent studies.
• Allopurinol : 20 mg/kg/day for 28 days
➢ A large placebo controlled double blinded study from
Colombia concluded that allopurinol monotherapy is
ineffective against Colombian cutaneous disease and
is unlikely to be effective against cutaneous disease
due to other organisms
➢ Combined therapy with allopurinol & meglumine
antimoniate has shown better response than either of
the two drugs used alone
JAAD 2002
63. TREATMENT
Oral Azoles
► Ketoconazole : 200-400 mg /day x 4 wks.
▪ 70% cure rate – L. major (Weinrauch et al)
▪ ineffective in – L. tropica and aethiopica.
▪ 89% cure rate – L. mexicana
► Itraconazole : 200 mg/ day x 4-8 wks
▪ 79% cure rate – old world CL (IJD – 1994)
▪ 66% cure rate from India (Dogra et al – IJD 1990)
64. TREATMENT
► TOPICAL AGENTS
► Topical paromomycin 15% in methylbenzethoniumchloride
applied twice daily for 10-30 days is effective in Israel in
L.major CL
► In open study, topical paromomycin was found to be
equally effective as i/l meglumine antimoniate for
treatment of L.major CL
Euj J Dermatol 2005
65. ► Pentamidine
► For cutaneous leishmaniasis the high cure rate associated with low
dose of pentamidine given for a shorter period makes it an
attractive alternative to sodium stibugluoconate and treatment of
choice in cases of Stibugluconate treatment failure.
► Pentamidine mesylate and isethionate are safe and effective drugs
in treatment of New World CL (Esther J.S. et al )
32/38 (84)2 mg/kg q.o.d., 4Open-label
nonrandomized
23/24 (96)2 mg/kg q.o.d., 7Open-label
nonrandomized
No. of patients cured/total
no. of patents (%)
Dosage/no. of
injections
Study design
Efficacy of pentamidine regimens for the treatment of cutaneous
leishmaniasis in Colombia.
67. TREATMENT
Miltefosine
► Phosphorylcholine ester of hexadecanol, a membrane
active alkylphospholipid
► First effective oral agent for VL, including antimony
resistant cases.
► Topical treatment with miltefosine has been shown to
efficiently reduce parasite load in experimental cutaneous
leishmaniasis.
► In an open label study in Colombia, 4 weeks treatment
with 133 and 150 mg of miltefosine daily cured 100% and
89% respectively – American cutaneous leishmaneasis
(Soto J et al 2001)
68. TREATMENT
► In a controlled study in Columbia & Guatemala, miltefosine
given in a dose of 2.5 mg/kg body weight for 28 days
produced 91% cure rate for L.panamensis infection and
50% cure rate for L. braziliensis & L. mexicana compared
to 38% & 20% for placebo respectively
► Was well tolerated, adverse effects seen were mostly
nausea, mild elevation in creatinine levels
Trans R Soc Trop Med Hyg. 2006
69. TREATMENT
► In a trial comparing the efficacy of miltefosine & sodium
stibugluconate in treatment of VL in an Ethopian population
with high prevelance of HIV infection, there was 88% initial
cure rate in both the groups, mortality was 2% & initial
treatment failure 8% with miltefosine compared to 8% &
1% resp with SSG
► Among HIV+ patients, cure rate, relapse rate & mortality in
miltefosine group was 60%, 10% & 6% compared to 65%,
2% & 12% with SSG.
► In HIV+ patients, miltefosine is a much safer, though
slightly less effective than SSG in treatment of leishmaniasis
Clin Infect Dis,2006
70. TREATMENT
Photodynamic Therapy
► In a randomized placebo controlled trial, efficacy of
Photodynamic therapy was compared with paromomycin &
placebo
► Group 1 was treated with weekly topical PDT, and groups 2
and 3 received twice-daily topical paromomycin and
placebo, respectively. The duration of treatment was 4
weeks for all groups. These groups were followed for 2
months after the end of treatment.
► At the end of the study, complete improvement was seen
in 29 of 31 (93.5%), 14 of 34 (41.2%) and 4 of 30 lesions
(13.3%) in groups 1, 2 and 3, respectively (P<0.001). At
the same time point, 100%, 64.7% and 20% of the lesions
had parasitological cure in group 1, 2 and 3, respectively
(P<0.001)
71. TREATMENT
Immunotherapy
• Interferon-γ – Intralesional treatment has been tried for
cutaneous lesions
➢ In one study in L. braziliensis infection, 12 of 13 lesions
became smaller after injection.
➢ IFN-γ was also compared with antomony.
▪ I/L infiltration once a week x 5 weeks
▪ 100% cure rate with antomony treated lesions Vs 38% of
IFN-γ treated lesions – L. tropica
• Recombinent IL-2 has been used to treat a few patients
with disseminated cutaneous leishmaniasis.
72. TREATMENT
Immunochemotherapy
In a double-blind placebo controlled study of 102 patients
with American CL, combination of a single –strain
leishmania amazonensis killed promastiote vaccine with
half dose of amtimonial – 100% cure rate after 4 series of
treatments [10-day series at an interval of 10 days]
compared to 82% in control group.
IJD 2002
73. TREATMENT
► Imiquimod
➢ Another topical agent under investigation for cutaneous
leishmaniasis
➢ Immunomodulator developed to geintal warts.
➢ It produced 90% cure rate in patients who had failed to
respond to antimonials alone when it was used in
conjunction with antimonials in peru. (Arevaloi et al)
Clin Infect Dis
2001
➢ 5% Imiquomod with or without I/L meglumine antimoniate
is more effective than I/L meglumine antimoniate alone in
treatment of old world CL
JAAD 2005
74. LEISHMANIASIS IN HIV INFECTION
► VL is the fourth most common opportunistic parasitic
disease in HIV-positive individuals
► VL promotes the development of AIDS-defining
conditions and HIV infection increases the
development of VL by 100-1000 times in endemic
areas, reduces the therapeutic response & increases
the relapse rate
► Leishmania/HIV co-infection has so far been reported
from 33 countries worldwide, most commonly from
Brazil (in Americas) and India ( in Asia)
► Introduction of HAART decreases the incidence of
leishmania infection in HIV positive patients
75. LEISHMANIASIS IN HIV INFECTION
► Cutaneous involvement is seen in 2-12% of patients
with leishmania/HIV co-infection
► Causes a variable spectrum of lesions – papular,
maculopapular & nodular
► Leishmania amastigotes have been found in
apparently normal skin, infestating sweat ducts, &
co-existing with lesions of KS, HSV & HZV
► Leishmania is also associated with changes
attributable to other dermatological processes like
dermatofibroma, psoriasis, Reiters disease, bacillary
angiomatosis, cryptococcosis & oral aphthae
76. LEISHMANIASIS IN HIV INFECTION
► Can present as dermatomyositis like eruption
➢ mucocutaneous & mucosal
leishmaniasis
➢ post kala-azar leishmaniasis
► Primary cutaneous lesions can visceralize in severely
immunodepressed patients
77. LEISHMANIASIS IN HIV INFECTION
DIAGNOSIS
► Gold standard for diagnosis of leishmsniasis in HIV infected
individuals remains the isolation or identification of parasite
from appropriate tissue
► Detection of leishmania amastigotes & antigens in
peripheral blood has sensitivity of 50% which increases to
70% after culture
► New PCR techniques like detecting highly variable regions
of kinetoplast DNA & nested PCR have a sensitivity of
95.45% in peripheral blood & 100% in bone marrow
78. LEISHMANIASIS IN HIV INFECTION
TREATMENT
► Duration of treatment has to be prolonged until 4 weeks
► More likely to suffer from adverse events
► Low rate of clinical & parasitological response – 60% with
antimonials or with amphoterecin B
► 25-60% patients experience relapse during first year after
completing treatment
► Combining antimonials with allopurinol/IFN-γ useful in
refractory cases or in relapses
79. LEISHMANIASIS IN HIV INFECTION
SECONDARY PROPHYLAXIS
► Antimonials 20 mg/kg once a month – some degree of
efficacy is seen
► Pentamidine every 3-4 weeks
► liposomal AMB every 2 weeks
► Allopurinol/ itraconazole
Usually withdrawn when CD4+ cell count > 200/µl
80. ► My references are :-
➢ Textbook of dermatology –Rook
Fitzpatrick
➢ J Postgrad Med 2003
➢ J Am Acad Dermatol 1994, 1996
➢ Clin Infect Dis. 1997, 2001, 2006
➢ Drugs 1998; 56: 1009-1018
➢ Int. J. Dermatol 1994, 1998, 2002
➢ Trans R Soc Trop Med Hyg. 2006
➢ Clin Exp Dermatol 2006