Leishmaniasis

1. Leishmaniasis By: Dr Osman Sadig

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

5- L tropica6- L major

7- L ethiopica8- L braziliensis

9- L mexicana

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

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.

-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)

- 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:

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.

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)

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.

Out breaks

- Mellut town1940

- Southern Fung1956

- Jum jum tribe1958 (Satti)

- Western Upper Nile19841994

- Gedarif state 1996200-

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

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

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

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.

- 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.

-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

Differential diagnosis

- Malaria must be ruled out

- Enteric fever

- H/S schistosomiasis- African trypansom

- Miliary Tb

- Brucellosis & relapsing fevers

- AIDS

- Liver abscess

- Histoplasmosis- infectious mononucleos

- Other causes of gross splenomegaly- Malnutrition

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

- 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

- 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

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.

-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.

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

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

-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

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

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

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

-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.

-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

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.

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.

-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

Causes of death in VL -intercurrent infection including HIV- hepatic failure- renal failure

- bleeding- malnutrition- severe anaemia

- cancrum oris- HF or cardiac arrest (SSG)

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 .

-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

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

Leishmaniasis

Health & Medicine

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