Download - Leishmaniasis
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- 1. Leishmaniasis By: Dr Osman Sadig
2.
- The leishmaniasisare a group of diseases
- with a variety ofclinical manifestations
- 1- Visceral leishmaniasisVL/ PKDL
- 2- Cutaneous leishmaniasisCL
- 3- Mucocutaneous leishmaniasisMCL
- 4- Diffuse cutaneous leishmaniasis DCL
- Over 20 pathogenic sp of leish parasites
- are known:
- 1- L donovani2- L infantum
- 3- L archibaldi4- L chagasi
3.
- 5- L tropica6- L major
- 7- L ethiopica8- L braziliensis
- 9- L mexicana
4. 5. 6.
- The outcome of the infection depends on :
- 1- Parasite invasiveness & pathogenicity
- 2- dose of inoculum
- 3- parasite tropism
- 4- genetically determined host immune
- responseA single leish sp can produce diff clinicalsyndromes and each of the syndromescan be caused by more than one sp e.g.Viscerotropic L tropica
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- Visceral leishmaniasis
- VL is usually fatal disease without TR.
- Epidemiology
- - About500 000new cases annually,90%
- inIndia & Sudan
- - Infection isendemicin India, China
- Central Asia, East Africa, Middle east,
- Medit region and Latin America
- - VL isendemic in Sudan& has been
- reported since early 19 thcentury.
8.
- -Main endemic areas in Sudan are :
- 1-Eastern Sudan along Atbara & Rahad
- rivers
- 2- Sinnar & Blue Nile states
- 3- Upper Nile state
- 4- Eastern Equatoria around Kapoita
- 5- South Kordofan
- 6- South Darfor
- -VL is caused by L. donovani (LDB),L. infantum, L. chagasi & L. tropica( usually mild disease)
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- - More than24 600cases &1193deaths
- had been reported in Sudan during
- 19962001. This is onlyreported cases
- and does not reflect actual dis transmiss
- - The dis affects mainlychildren & young
- adultsand is commoner amongpoorpeople, farmers, labourers,malnourished, people visiting endemicareas for the 1 sttime and intheimmunosuppressed
- - Leishmania exists in 2 different forms:
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- Leishmania exists in 2 different forms :
- 1-Promastigotein the vector developing
- from amastigotes through series of
- intermediate stages in thedigestive tract
- eventually migrating to theproboscisand
- inoculated to the skin of the host withthe blood meal. It ispearl or spindleshaped 1015 mc withflagellum .
- 2-Amastigote : develops in the human-being from promastigote & proliferate
- in theR/E systemwithin macrophages.It isovalin shape.
11. 12. 13.
- The vectorisFemale sand fly-Phlebotomus orientalis
- - Phl martini(termite hill dweller)
- - Phl lutzomyia in new world leishma
- The reservoir
- - Depends on the leish sp & the vector
- -Rodents, dogs, wild animals &patients
- with VL (PKDL)
14. 15.
- Transmission
- Depends on the presence of suitablereservoir ,vectorand susceptible humanhost
- 1- H uman to human ( anthroponotic)e.g.India (causing epidemics)
- 2- A nimal reservoir to human ( zoonotictransmission)e.g. dogs in the MEand Mediterranean where the dis. issporadic in children and opportunisticin immunosuppressed HIV patients
- 3-Congenital, sexual & BT are rare.
16.
- Out breaks
- - Mellut town1940
- - Southern Fung1956
- - Jum jum tribe1958 (Satti)
- - Western Upper Nile19841994
- - Gedarif state 1996200-
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- Immunity
- Out come of infection depends on the
- interplay betweenprotective CMIrespon
- at one hand &dis enhancing immune
- response on the other hand
- 1- Th1 CD4 cellsare protective by
- producing IL2 & INF gamma which
- stimulate macrophage to inhibit the
- growth of amastigotes
- 2- Th2 CD4 cellsproduce IL4,5 which
- enhance disease progression
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- Leishmania infection results in life long latent immunity. With immunoparesis leishmania can become opportunistic pathogen through reactivation or new infection .
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- Clinical manifestations
- - Varies fromasymptomatic self limitting
- dis tofrank VL which is fatal if untreated ,
- with mild dis in between.
- 1-Clinically suspect caseis any pat who
- lives or had traveled to an endemic area
- presenting with fever of > 2/52+ spleenomegaly and/orLymphadenopathy in whom malaria isruled out or treated
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- 2 - Probable case : suspect case +leucopenia
- 3 - Confirmed case : suspect case +positive parasitology
- Presentation
- - IP : 12/12 (2/5210 years)
- - Onset : insidious , but may be acute
- - Fever (95%) : prolonged fever without rig
- It may be intermittent, remittent wz doubl
- spike or contin. Fever is well tolerated.
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- - Splenomegaly(95%)
- - Wt loss(80%) & wasting later
- - Anaemia(75%):chronic dis, bleeding,
- hemolysis, BM infilt wz parasites, hypresp
- haemodilution.
- - Hepatomegaly (60%)- LN (75%)
- - cough (75%)- anorexia (70%)
- - epistaxis (50%)- diarhoea (40%)
- - vomiting (15%)- jaundice (5%)
- - edema (5%)- ascites.
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- -skin pigmentation : The skin is dry, thin,scaly with sparse hair.
- Atypical casespresent with:- mild symptoms and/or isolatedsplenomegaly
- - lymphadenopathy may be the sole
- presentation in India
- - Some present with PKDL
- - Some show sub clinical sero conversion
- - Inimmunosuppressed (e.g AIDS)feverand spleenomegaly may be absent
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- Differential diagnosis
- - Malaria must be ruled out
- - Enteric fever
- - H/S schistosomiasis- African trypansom
- - Miliary Tb
- - Brucellosis & relapsing fevers
- - AIDS
- - Liver abscess
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- - Histoplasmosis- infectious mononucleos
- - Other causes of gross splenomegaly- Malnutrition
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- Laboratory & diagnosis:
- - CBC & ESR:
- - anaemia (60-90%)
- - leucopenia (84%)
- - thrombocytopenia (73%)
- - high ESR
- - Liver biochemstry:
- albumin < 30 g/l (88%), globulin >30g/l (78%), elevated ser bilirubin,transaminases and ALP
- - Renal profile & ECG
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- - Specific diagnosis depends on clinicalsuspicion & either 1-parasitologyOR2-serology .
- 1- Parasitology : specimen obtained from:
- - Gland punctureis easy & safe with
- 5065% sensitivity
- - BM aspiraterequire trained person,
- painful & require sp needle wz
- 6492% sensitivity
- - Splenic puncture : invasive & hazardous
- with 9095% sensitivity
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- - rarely from puffy coat layer of blood- Culture in NNN media
- * Negative splenic aspirate does not
- exclude diagnosis
- *Parasitology is the only diagnosticmethod in relapse, HIV pat & infants< 6/12
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- 2- Serology : in clinically suspected cases
- (FAT, DAT, ELIZA, Latex Agg test, PCR)
- -DATissensitive, specific, simpleand
- can be easily performed under field
- conditions, but needs trained staff.
- Not useful for relapse diagn or TOC. Positive DAT(>1:64000) combinedwithnegative LSTin a clinicalsuspect isdiagnostic.Positive LSTrules out active VL even if DAT ispositive.
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- -Katexdetects Ag in urine, sensitive andspecific
- -ICT 3 LST: measurestype 1V hypersensitivity .
- It is negative in active VL, but becomes
- positive in 80% 36 months after TR
- It isvaluable in epidemiological studies and augments DAT in the diagnosis if itis negative.
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- Treatment of VL:( supportive/ specific)
- - TR ideally given toconfirmed casesin
- hospital settingsundermed supervision
- -Trial of TR is only consideredif there are
- no lab. facilities & after exclusion of
- other infections and occasionally in
- highly suspected cases despite Ve lab.
- 1- Supportive TRinclude nutritional care,
- oral hygiene, Fe, folic acid, multivit, TR
- of infections, BT & correction of flu & E
31.
- 2- Specific TR :-
- A- First line drugs:
- 1 - Sod stibogluconateis pentavalantimony (SSG) in 100mg/ml. Dose20mg/kg/dIV or IM for 30 days.
- -SE:include A,N,V, fatigue, headachearthralgia myalgia, cough,cardiotoxicity, renal damage
- pancreatitis, elevated ser amylase andtransaminases, and local pain
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- -CI : cardiac dis, liver dis, renal fail,
- moribund pat & full blown AIDS.
- 2- Meglumine antimoniateis similar to SSG
- but in 85 mg/ ml
- B- Second line drugs :
- 1- Amphotericin B1mg/kg EOD for 30days Nephrotoxic. 2 ndline drug.2 - Ambisome(amphotericin B lipidcomplex) is alternative 1 stline drug.50 dollars for 50 mg vial & 600 dollarstotal TR.Dose2030 mg/kg over2/52 in doses of 35 mg/ kg with
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- TOC in day 21. It is reconstituted anddiluted in 5% dextrose and infusedover 306o min.Main indications of ambisome are:-unresponsiveness to SSG- 3 rdrelapse
- - cardiac disease- hepatic & renal impairment
- - moribund patients .3- Pentamidine34 mg/kg EOD for 10doses 2 ndline drug
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- 4- Paromomycin(aminosidine) 15mg/kgfor 17 days IM or IV diluted in NSover 90 min. Usually used in combinwith SSG. Oto/ Nephrotoxic.
- 5- Miltefosine : anti neoplastic.Oral,sp
- used in India
- 6- Allopurinol7- ketoconazole8- INF gamma
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- Follow up:
- - gen condition, temp, spleen, Wt, CBC
- - TOCat 2530 dayof TR to asses theparasitologicalcure. GP in routine use. -Initial cure= clinical cure + parasitologic
- cure by the end of TR
- -Definite cure= absence of symptoms
- and signs 6/12 after initial cure
- -Follow upat 3, 6, 12 M & if symptoms rec
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- -slow responder= pat with no clinical
- response & low grade parasitaemia
- after 30/d of TR. Extend TR to 60 days or
- until 2 consecutive ve TOC-Non responder = patient with no clinical
- response & high grade parasitology after
- 30 days TR with SSG. Combine SSG +paramomycin OR go to ambisome forTR.
37.
- -Relapse(5%) = pat with clinical andparasitological confirmed case & pasthistory of TR of VL.1 st, 2 ndand 3 rdrelapse -For 1 strelapse:SSG for 60 days or till
- 2 consecutive ve TOC ORSSG + paramomycin
- -For 2 ndrelapse:SSG + parmomycin OR
- go to ambisome
- -For 3 rdrelapseambisomeScreen for HIV for non resp and relapse cases
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- Complications of VL
- - Intercurrent infections(Tb, otitis M, canc
- oris, pyoderma, viral)
- -Malnutrition & anaemia
- - Bleeding, hepatic failure
- - Neurological(P. neuropathy, GB, ataxia
- myelopathy, deafness)
- - PKDL : usually follows TR but can occur
- during TR or wz out history of clinical VL.
39.
- PKDL - grade 1 PKDL = rash on the face +/-
- upper chest & arms
- - grade 2 PJDL = dense rash most of the
- face, on the trunk, arm & legs.
- When extensive & black nodule = grade
- 2 severe
- - grade 3 = dense rash most of the body
- including hands & feet. Ulceration, crust
- scaling & mucosal spread (PKML) can
- occur.
40. 41. 42.
- -Parasites are scantyin PKDL which mayserve as a reservoir of infection- PKDL should be differentiated from L. leprosy, measels, fungal infections,syphilis, yaws & T versecolor
- - TRis given for grade 3 & 2 severe. Dose20 mg/k SSG daily till clinical cure up to2/12
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- Causes of death in VL -intercurrent infection including HIV- hepatic failure- renal failure
- - bleeding- malnutrition- severe anaemia
- - cancrum oris- HF or cardiac arrest (SSG)
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- VL & HIV Co infection
- - Both are associated wzimmune suppres
- andpotentiate each other-Suspectedin VL pat wzhighparasitaemia ,non responders& inrelapsers
- -Clinical diagn may be diff . Fever, spleno
- and pancytopenia may not be present
- and clinical suspicion may beobscuredby opportunistic infections .Presentation may beatypical .
45.
- -VL may be rapidly progressive& may
- have predominant GIT symptoms-CD4 < 200&associated opportunistic
- infections are common-Serology is ve in up to 50%due to
- depressed immune response
- -Diagn by parasitology . Parasitesare
- abundant in LN or BM aspirates. It is +vein 50% in thebuffy coat of blood
- -TR is diff. Relapse rate & mortality high
46.
- anddrug SE are more severe .-Combined anti leish & anti retroviral
- drugs for TR.
- - Response to anti leishmanial TR is poor
- due to depressed immune resp & increas
- parasite load. Relapse in 50% & relapses
- should only be treated if symptoms are
- severe