Leishmaniasis

1. LeishmaniasisLeishmaniasis
By: Dr Osman SadigBy: Dr Osman Sadig

2. The leishmaniasisThe leishmaniasis are a group of diseases are a group of diseases
with a variety of with a variety of clinical manifestationsclinical manifestations
1- Visceral leishmaniasis VL/ PKDL1- Visceral leishmaniasis VL/ PKDL
2- Cutaneous leishmaniasis CL2- Cutaneous leishmaniasis CL
3- Mucocutaneous leishmaniasis MCL3- Mucocutaneous leishmaniasis MCL
4- Diffuse cutaneous leishmaniasis DCL4- Diffuse cutaneous leishmaniasis DCL
Over 20 pathogenic sp of leish parasites Over 20 pathogenic sp of leish parasites
are known:are known:
1- L donovani 2- L infantum 1- L donovani 2- L infantum
3- L archibaldi 4- L chagasi 3- L archibaldi 4- L chagasi

3. 5- L tropica 6- L major 5- L tropica 6- L major
7- L ethiopica 8- L braziliensis7- L ethiopica 8- L braziliensis
9- L mexicana9- L mexicana

6. The outcome of the infection depends onThe outcome of the infection depends on::
1- Parasite invasiveness & pathogenicity1- Parasite invasiveness & pathogenicity
2- dose of inoculum2- dose of inoculum
3- parasite tropism3- parasite tropism
4- genetically determined host immune4- genetically determined host immune
response response
A single leish sp can produce diff clinical A single leish sp can produce diff clinical
syndromes and each of the syndromes syndromes and each of the syndromes
can be caused by more than one sp e.g. can be caused by more than one sp e.g.
Viscerotropic L tropica Viscerotropic L tropica

7. Visceral leishmaniasisVisceral leishmaniasis
VL is usually fatal disease without TR.VL is usually fatal disease without TR.
EpidemiologyEpidemiology
- About - About 500 000500 000 new cases annually, new cases annually, 90%90%
in in India & SudanIndia & Sudan
- Infection is - Infection is endemicendemic in India, China in India, China
Central Asia, East Africa, Middle east,Central Asia, East Africa, Middle east,
Medit region and Latin AmericaMedit region and Latin America
- VL is - VL is endemic in Sudanendemic in Sudan & has been & has been
reported since early 19reported since early 19
thth
century. century.

8. - - Main endemic areas in Sudan areMain endemic areas in Sudan are::
1- 1- Eastern Sudan along Atbara & RahadEastern Sudan along Atbara & Rahad
riversrivers
2- Sinnar & Blue Nile states2- Sinnar & Blue Nile states
3- Upper Nile state3- Upper Nile state
4- Eastern Equatoria around Kapoita4- Eastern Equatoria around Kapoita
5- South Kordofan5- South Kordofan
6- South Darfor6- South Darfor
- - VL is caused by L. donovani (LDB), VL is caused by L. donovani (LDB),
L. infantum, L. chagasi & L. tropica L. infantum, L. chagasi & L. tropica
( (usually mild disease)usually mild disease)

9. - More than - More than 24 60024 600 cases & cases & 11931193 deaths deaths
had been reported in Sudan duringhad been reported in Sudan during
1996—2001. This is only 1996—2001. This is only reported casesreported cases
and does not reflect actual dis transmissand does not reflect actual dis transmiss
- The dis affects mainly - The dis affects mainly children & youngchildren & young
adultsadults and is commoner among and is commoner among poor poor
people, farmers, labourers, people, farmers, labourers,
malnourished, people visiting endemic malnourished, people visiting endemic
areas for the 1 areas for the 1
stst
time and in the time and in the
immunosuppressed immunosuppressed
- Leishmania exists in 2 different forms:- Leishmania exists in 2 different forms:

10. Leishmania exists in 2 different formsLeishmania exists in 2 different forms::
1- 1- PromastigotePromastigote in the vector developing in the vector developing
from amastigotes through series offrom amastigotes through series of
intermediate stages in the intermediate stages in the digestive tractdigestive tract
eventually migrating to the eventually migrating to the proboscisproboscis and and
inoculated to the skin of the host with inoculated to the skin of the host with
the blood meal. It is the blood meal. It is pearl or spindle pearl or spindle
shaped 10—15 mc with shaped 10—15 mc with flagellumflagellum. .
2- 2- AmastigoteAmastigote: develops in the human- : develops in the human-
being from promastigote & proliferate being from promastigote & proliferate
in the in the R/E systemR/E system within macrophages. within macrophages.
It is It is ovaloval in shape. in shape.

13. The vectorThe vector is is Female sand fly Female sand fly
- - Phlebotomus orientalisPhlebotomus orientalis
- Phl martini- Phl martini (termite hill dweller) (termite hill dweller)
- Phl lutzomyia in new world leishma- Phl lutzomyia in new world leishma
The reservoirThe reservoir
- Depends on the leish sp & the vector- Depends on the leish sp & the vector
- - Rodents, dogs, wild animals & Rodents, dogs, wild animals & patientspatients
with VL (PKDL)with VL (PKDL)

15. TransmissionTransmission
Depends on the presence of suitable Depends on the presence of suitable
reservoirreservoir, , vectorvector and susceptible human and susceptible human
hosthost
1- H1- Human to human (uman to human (anthroponotic)anthroponotic) e.g. e.g.
India (causing epidemics) India (causing epidemics)
2- A2- Animal reservoir to human (nimal reservoir to human (zoonotic zoonotic
transmission) transmission) e.g. dogs in the ME e.g. dogs in the ME
and Mediterranean where the dis. is and Mediterranean where the dis. is
sporadic in children and opportunistic sporadic in children and opportunistic
in immunosuppressed – HIV patientsin immunosuppressed – HIV patients
3- 3- Congenital, sexual & BT are rare. Congenital, sexual & BT are rare.

16. Out breaksOut breaks
- Mellut town 1940- Mellut town 1940
- Southern Fung 1956- Southern Fung 1956
- Jum jum tribe 1958 (Satti)- Jum jum tribe 1958 (Satti)
- Western Upper Nile 1984—1994 - Western Upper Nile 1984—1994
- Gedarif state 1996—200-- Gedarif state 1996—200-

17. ImmunityImmunity
Out come of infection depends on theOut come of infection depends on the
interplay between interplay between protective CMIprotective CMI respon respon
at one hand & at one hand & dis enhancing immunedis enhancing immune
response on the other handresponse on the other hand
1- Th1 CD4 cells1- Th1 CD4 cells are protective by are protective by
producing IL2 & INF gamma whichproducing IL2 & INF gamma which
stimulate macrophage to inhibit thestimulate macrophage to inhibit the
growth of amastigotesgrowth of amastigotes
2- Th2 CD4 cells2- Th2 CD4 cells produce IL4,5 which produce IL4,5 which
enhance disease progressionenhance disease progression

18. Leishmania infection results in life long Leishmania infection results in life long
latent immunity. With immunoparesis latent immunity. With immunoparesis
leishmania can become opportunistic leishmania can become opportunistic
pathogen through reactivation or new pathogen through reactivation or new
infectioninfection..

19. Clinical manifestationsClinical manifestations
- Varies from - Varies from asymptomatic self limittingasymptomatic self limitting
dis to dis to frank VL which is fatal if untreatedfrank VL which is fatal if untreated,,
with mild dis in between.with mild dis in between.
1- 1- Clinically suspect caseClinically suspect case is any pat who is any pat who
lives or had traveled to an endemic arealives or had traveled to an endemic area
presenting with fever of > 2/52 presenting with fever of > 2/52
+ spleenomegaly and/or + spleenomegaly and/or
Lymphadenopathy in whom malaria is Lymphadenopathy in whom malaria is
ruled out or treated ruled out or treated

20. 22- Probable case- Probable case: suspect case + : suspect case +
leucopenialeucopenia
33- Confirmed case- Confirmed case: suspect case + : suspect case +
positive parasitologypositive parasitology
PresentationPresentation
- IP- IP: 1—2/12 (2/52—10 years): 1—2/12 (2/52—10 years)
- Onset- Onset: insidious , but may be acute: insidious , but may be acute
- Fever (95%)- Fever (95%): prolonged fever without rig: prolonged fever without rig
It may be intermittent, remittent wz doublIt may be intermittent, remittent wz doubl
spike or contin. Fever is well tolerated.spike or contin. Fever is well tolerated.

21. - Splenomegaly- Splenomegaly (95%) (95%)
- Wt loss- Wt loss (80%) & wasting later (80%) & wasting later
- Anaemia- Anaemia (75%): chronic dis, bleeding, (75%): chronic dis, bleeding,
hemolysis, BM infilt wz parasites, hypresphemolysis, BM infilt wz parasites, hypresp
haemodilution.haemodilution.
- Hepatomegaly (60%) - LN (75%)- Hepatomegaly (60%) - LN (75%)
- cough (75%) - anorexia (70%)- cough (75%) - anorexia (70%)
- epistaxis (50%) - diarhoea (40%)- epistaxis (50%) - diarhoea (40%)
- vomiting (15%) - jaundice (5%)- vomiting (15%) - jaundice (5%)
- edema (5%) - ascites. - edema (5%) - ascites.

22. - - skin pigmentationskin pigmentation: The skin is dry, thin, : The skin is dry, thin,
scaly with sparse hair. scaly with sparse hair.
Atypical casesAtypical cases present with: present with:
- mild symptoms and/or isolated - mild symptoms and/or isolated
splenomegaly splenomegaly
- lymphadenopathy may be the sole - lymphadenopathy may be the sole
presentation in Indiapresentation in India
- Some present with PKDL- Some present with PKDL
- Some show sub clinical sero conversion- Some show sub clinical sero conversion
- In - In immunosuppressed (e.g AIDS)immunosuppressed (e.g AIDS) fever fever
and spleenomegaly may be absent and spleenomegaly may be absent

23. Differential diagnosisDifferential diagnosis
- Malaria must be ruled out- Malaria must be ruled out
- Enteric fever- Enteric fever
- H/S schistosomiasis - H/S schistosomiasis
- African trypansom - African trypansom
- Miliary Tb- Miliary Tb
- Brucellosis & relapsing fevers- Brucellosis & relapsing fevers
- AIDS- AIDS
- Liver abscess- Liver abscess

24. - Histoplasmosis - Histoplasmosis
- infectious mononucleos - infectious mononucleos
- Other causes of gross splenomegaly - Other causes of gross splenomegaly
- Malnutrition - Malnutrition

25. Laboratory & diagnosis:Laboratory & diagnosis:
- CBC & ESR:- CBC & ESR:
- anaemia (60-90%)- anaemia (60-90%)
- leucopenia (84%)- leucopenia (84%)
- thrombocytopenia (73%)- thrombocytopenia (73%)
- high ESR- high ESR
- Liver biochemstry:- Liver biochemstry:
albumin < 30 g/l (88%), globulin >30 albumin < 30 g/l (88%), globulin >30
g/l (78%), elevated ser bilirubin, g/l (78%), elevated ser bilirubin,
transaminases and ALP transaminases and ALP
- Renal profile & ECG- Renal profile & ECG

26. - Specific diagnosis depends on clinical - Specific diagnosis depends on clinical
suspicion & either 1- suspicion & either 1- parasitologyparasitology OR OR
2- 2- serologyserology..
1- Parasitology1- Parasitology: specimen obtained from:: specimen obtained from:
- Gland puncture- Gland puncture is easy & safe with is easy & safe with
50—65% sensitivity50—65% sensitivity
- BM aspirate- BM aspirate require trained person, require trained person,
painful & require sp needle wzpainful & require sp needle wz
64—92% sensitivity64—92% sensitivity
- Splenic puncture- Splenic puncture: invasive & hazardous: invasive & hazardous
with 90—95% sensitivitywith 90—95% sensitivity

27. - rarely from puffy coat layer of blood - rarely from puffy coat layer of blood
- Culture in NNN media - Culture in NNN media
* Negative splenic aspirate does not * Negative splenic aspirate does not
exclude diagnosis exclude diagnosis
* * Parasitology is the only diagnostic Parasitology is the only diagnostic
method in relapse, HIV pat & infants method in relapse, HIV pat & infants
< 6/12 < 6/12

28. 2- Serology2- Serology: in clinically suspected cases: in clinically suspected cases
(FAT, DAT, ELIZA, Latex Agg test, PCR)(FAT, DAT, ELIZA, Latex Agg test, PCR)
- - DAT DAT is is sensitive, specific, simplesensitive, specific, simple and and
can be easily performed under fieldcan be easily performed under field
conditions, but needs trained staff.conditions, but needs trained staff.
Not useful for relapse diagn or TOC.Not useful for relapse diagn or TOC.
Positive DATPositive DAT (>1:64000) combined (>1:64000) combined
with with negative LSTnegative LST in a clinical in a clinical
suspect is suspect is diagnostic.diagnostic. Positive LST Positive LST
rules out active VL even if DAT is rules out active VL even if DAT is
positive. positive.

29. - - KatexKatex detects Ag in urine, sensitive and detects Ag in urine, sensitive and
specific specific
- - ICT 3ICT 3
LST:LST:
measures measures type 1V hypersensitivitytype 1V hypersensitivity..
It is negative in active VL, but becomesIt is negative in active VL, but becomes
positive in 80% 3—6 months after TRpositive in 80% 3—6 months after TR
It is It is valuable in epidemiological studiesvaluable in epidemiological studies
and augments DAT in the diagnosis if it and augments DAT in the diagnosis if it
is negative. is negative.

30. Treatment of VL: Treatment of VL: ((supportive/ specific)supportive/ specific)
- TR ideally given to - TR ideally given to confirmed casesconfirmed cases in in
hospital settingshospital settings under under med supervisionmed supervision
- - Trial of TRTrial of TR is only consideredis only considered if there are if there are
no lab. facilities & after exclusion ofno lab. facilities & after exclusion of
other infections and occasionally inother infections and occasionally in
highly suspected cases despite –Ve lab.highly suspected cases despite –Ve lab.
1- Supportive TR1- Supportive TR include nutritional care, include nutritional care,
oral hygiene, Fe, folic acid, multivit, TR oral hygiene, Fe, folic acid, multivit, TR
of infections, BT & correction of flu & Eof infections, BT & correction of flu & E

31. 2- Specific TR2- Specific TR:-:-
A- First line drugs:A- First line drugs:
11- Sod stibogluconate- Sod stibogluconate is pentaval is pentaval
antimony (SSG) in 100mg/ml. Dose antimony (SSG) in 100mg/ml. Dose 20 20
mg/kg/d mg/kg/d IV or IM for 30 days. IV or IM for 30 days.
- - SE:SE: include A,N,V, fatigue, headache include A,N,V, fatigue, headache
arthralgia myalgia, cough, arthralgia myalgia, cough,
cardiotoxicity, renal damage cardiotoxicity, renal damage
pancreatitis, elevated ser amylase and pancreatitis, elevated ser amylase and
transaminases, and local pain transaminases, and local pain

32. - - CICI: cardiac dis, liver dis, renal fail,: cardiac dis, liver dis, renal fail,
moribund pat & full blown AIDS.moribund pat & full blown AIDS.
2- Meglumine antimoniate2- Meglumine antimoniate is similar to SSG is similar to SSG
but in 85 mg/ ml but in 85 mg/ ml
B- Second line drugsB- Second line drugs: :
1- Amphotericin B1- Amphotericin B 1mg/kg EOD for 30 1mg/kg EOD for 30
days Nephrotoxic. 2 days Nephrotoxic. 2
ndnd
line drug. line drug.
22- Ambisome- Ambisome (amphotericin B lipid (amphotericin B lipid
complex) is alternative 1 complex) is alternative 1
stst
line drug. line drug.
50 dollars for 50 mg vial & 600 dollars 50 dollars for 50 mg vial & 600 dollars
total TR. total TR. DoseDose 20—30 mg/kg over 20—30 mg/kg over
2/52 in doses of 3—5 mg/ kg with 2/52 in doses of 3—5 mg/ kg with

33. TOC in day 21. It is reconstituted and TOC in day 21. It is reconstituted and
diluted in 5% dextrose and infused diluted in 5% dextrose and infused
over 30—6o min. over 30—6o min.
Main indications of ambisome are: Main indications of ambisome are:
- - unresponsiveness to SSG unresponsiveness to SSG
- 3 - 3
rdrd
relapse relapse
- cardiac disease - cardiac disease
- hepatic & renal impairment - hepatic & renal impairment
- moribund patients- moribund patients. .
3- Pentamidine3- Pentamidine 3—4 mg/kg EOD for 10 3—4 mg/kg EOD for 10
doses 2 doses 2
ndnd
line drug line drug

34. 4- Paromomycin4- Paromomycin (aminosidine) 15mg/kg (aminosidine) 15mg/kg
for 17 days IM or IV diluted in NS for 17 days IM or IV diluted in NS
over 90 min. Usually used in combin over 90 min. Usually used in combin
with SSG. Oto/ Nephrotoxic. with SSG. Oto/ Nephrotoxic.
5- Miltefosine5- Miltefosine: anti neoplastic. : anti neoplastic. Oral,Oral, sp sp
used in Indiaused in India
6- Allopurinol 6- Allopurinol
7- ketoconazole 7- ketoconazole
8- INF gamma 8- INF gamma

35. Follow up:Follow up:
- gen condition, temp, spleen, Wt, CBC- gen condition, temp, spleen, Wt, CBC
- TOC - TOC at 25—30 dayat 25—30 day of TR to asses the of TR to asses the
parasitological parasitological cure. GP in routine use. - cure. GP in routine use. -
Initial cureInitial cure = clinical cure + parasitologic = clinical cure + parasitologic
cure by the end of TRcure by the end of TR
- - Definite cureDefinite cure = absence of symptoms = absence of symptoms
and signs 6/12 after initial cureand signs 6/12 after initial cure
- - Follow upFollow up at 3, 6, 12 M & if symptoms rec at 3, 6, 12 M & if symptoms rec

36. - - slow responderslow responder = pat with no clinical = pat with no clinical
response & low grade parasitaemiaresponse & low grade parasitaemia
after 30/d of TR. Extend TR to 60 days orafter 30/d of TR. Extend TR to 60 days or
until 2 consecutive –ve TOC until 2 consecutive –ve TOC
- - Non responderNon responder= patient with no clinical= patient with no clinical
response & high grade parasitology afterresponse & high grade parasitology after
30 days TR with SSG. Combine SSG + 30 days TR with SSG. Combine SSG +
paramomycin OR go to ambisome for paramomycin OR go to ambisome for
TR. TR.

37. - - Relapse Relapse (5%)(5%) = pat with clinical and = pat with clinical and
parasitological confirmed case & past parasitological confirmed case & past
history of TR of VL. history of TR of VL. 11
stst
, 2 , 2
ndnd
and 3 and 3
rdrd
relapse relapse
- - For 1For 1
stst
relapse: relapse: SSG for 60 days or till SSG for 60 days or till
2 consecutive –ve TOC OR 2 consecutive –ve TOC OR
SSG + paramomycin SSG + paramomycin
- - For 2For 2
ndnd
relapse: relapse: SSG + parmomycin OR SSG + parmomycin OR
go to ambisomego to ambisome
- - For 3For 3
rdrd
relapse relapse ambisome ambisome
Screen for HIV for non resp and Screen for HIV for non resp and
relapse casesrelapse cases

38. Complications of VLComplications of VL
- Intercurrent infections- Intercurrent infections (Tb, otitis M, canc (Tb, otitis M, canc
oris, pyoderma, viral)oris, pyoderma, viral)
- - Malnutrition & anaemiaMalnutrition & anaemia
- Bleeding, hepatic failure- Bleeding, hepatic failure
- Neurological- Neurological (P. neuropathy, GB, ataxia (P. neuropathy, GB, ataxia
myelopathy, deafness)myelopathy, deafness)
- PKDL- PKDL: usually follows TR but can occur: usually follows TR but can occur
during TR or wz out history of clinical VL. during TR or wz out history of clinical VL.

39. PKDLPKDL
- grade 1 PKDL = rash on the face +/- - grade 1 PKDL = rash on the face +/-
upper chest & armsupper chest & arms
- grade 2 PJDL = dense rash most of the- grade 2 PJDL = dense rash most of the
face, on the trunk, arm & legs.face, on the trunk, arm & legs.
When extensive & black nodule = gradeWhen extensive & black nodule = grade
2 severe2 severe
- grade 3 = dense rash most of the body- grade 3 = dense rash most of the body
including hands & feet. Ulceration, crustincluding hands & feet. Ulceration, crust
scaling & mucosal spread (PKML) can scaling & mucosal spread (PKML) can
occur. occur.

42. - - Parasites are scantyParasites are scanty in PKDL which may in PKDL which may
serve as a reservoir of infection serve as a reservoir of infection
- PKDL should be differentiated from- PKDL should be differentiated from
L. leprosy, measels, fungal infections, L. leprosy, measels, fungal infections,
syphilis, yaws & T versecolorsyphilis, yaws & T versecolor
- TR- TR is given for grade 3 & 2 severe. Dose is given for grade 3 & 2 severe. Dose
20 mg/k SSG daily till clinical cure up to 20 mg/k SSG daily till clinical cure up to
2/12 2/12

43. Causes of death in VLCauses of death in VL
- - intercurrent infection including HIV intercurrent infection including HIV
- hepatic failure - hepatic failure
- renal failure - renal failure
- bleeding - bleeding
- malnutrition - malnutrition
- severe anaemia - severe anaemia
- cancrum oris - cancrum oris
- HF or cardiac arrest (SSG) - HF or cardiac arrest (SSG)

44. VL & HIV Co infectionVL & HIV Co infection
- Both are associated wz - Both are associated wz immune suppresimmune suppres
and and potentiate each other potentiate each other
- - SuspectedSuspected in VL pat wz in VL pat wz high high
parasitaemia parasitaemia, , non respondersnon responders & in & in
relapsersrelapsers
- - Clinical diagn may be diffClinical diagn may be diff. Fever, spleno. Fever, spleno
and pancytopenia may not be presentand pancytopenia may not be present
and clinical suspicion may be and clinical suspicion may be obscured obscured
by opportunistic infections by opportunistic infections. .
Presentation may be Presentation may be atypicalatypical..

45. - - VL may be rapidly progressiveVL may be rapidly progressive & may & may
have predominant GIT symptoms have predominant GIT symptoms
- - CD4 < 200CD4 < 200 & & associated opportunisticassociated opportunistic
infections are common infections are common
- - Serology is –ve in up to 50%Serology is –ve in up to 50% due to due to
depressed immune responsedepressed immune response
- - Diagn by parasitologyDiagn by parasitology. Parasites are . Parasites are
abundant in LN or BM aspirates. It is +ve abundant in LN or BM aspirates. It is +ve
in 50% in the in 50% in the buffy coat of bloodbuffy coat of blood
- - TR is diff. Relapse rate & mortality highTR is diff. Relapse rate & mortality high

46. and and drug SE are more severedrug SE are more severe. .
- - Combined anti leish & anti retroviral Combined anti leish & anti retroviral
drugs for TR.drugs for TR.
- Response to anti leishmanial TR is poor - Response to anti leishmanial TR is poor
due to depressed immune resp & increasdue to depressed immune resp & increas
parasite load. Relapse in 50% & relapsesparasite load. Relapse in 50% & relapses
should only be treated if symptoms areshould only be treated if symptoms are
severesevere