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
7.
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)
9.
- 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:
10.
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-
17.
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
18.
Leishmania infection results in life long latent immunity. With
immunoparesis leishmania can become opportunistic pathogen through
reactivation or new infection .
19.
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
20.
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.
21.
- 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.
22.
-skin pigmentation : The skin is dry, thin,scaly with sparse
hair.
- Inimmunosuppressed (e.g AIDS)feverand spleenomegaly may be
absent
23.
Differential diagnosis
- Malaria must be ruled out
- Enteric fever
- H/S schistosomiasis- African trypansom
- Miliary Tb
- Brucellosis & relapsing fevers
- AIDS
- Liver abscess
24.
- Histoplasmosis- infectious mononucleos
- Other causes of gross splenomegaly- Malnutrition
25.
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
26.
- 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
27.
- 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
28.
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.
29.
-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.
30.
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.
pancreatitis, elevated ser amylase andtransaminases, and local
pain
32.
-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
33.
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
34.
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
35.
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
36.
-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
38.
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
43.
Causes of death in VL -intercurrent infection including HIV-
hepatic failure- renal failure
- bleeding- malnutrition- severe anaemia
- cancrum oris- HF or cardiac arrest (SSG)
44.
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