kalaazar

1. LEISHMANIASIS
DR.MOHAMMED SHANIL.P
JR1,GENERAL MEDICINE

2.  HISTORY
 EPIDEMIOLOGY
 MORPHOLOGY
 LIFE CYCLE
 IMMUNOPATHOGENESIS
 CLINICAL FEATURES
 LAB DIAGNOSIS
 TREATMENT
 PREVENTION

3. SIR WILLIAM LEISHMAN
1900 – SIR WILLIAM LEISHMAN
DISCOVERED L. DONOVANI IN
SPLEEN SMEARS OF A SOLDIER WHO
DIED OF FEVER AT DUM-DUM, INDIA.
THE DISEASE WAS KNOWN LOCALLY
AS DUM-DUM FEVER OR KALA-
AZAR.

4. LEISHMANIASIS
• UNICELLULAR EUKARYOTIC OBLIGATORY INTRACELLULAR
PROTOZOA
• CLINICAL SYNDROME
• SELF HEALING CUTANEOUS ULCER TO FATAL VISCERAL DISEASE
• 3 CATEGORIES VISCERAL ,CUTANEOUS,MUCOSAL

5. ETIOLOGY
• PHYLUM
• ORDER
• FAMILY
• GENUS
Sarcomastigophora
Kinetoplastida
Trypanosomatidae
Leishmania

6. VECTOR
• PHLEBOTOMOUS IN THE OLD WORLD
• LUTZOMYIA IN THE NEW WORLD
• FEMALE SANDFLIES BITE DURING NIGHT
• HUMANS ARE INCIDENTAL HOSTS

7. • LEISHMANIA DONOVANI(COMPLEX) (VL)
• LEISHMANIA TROPICA (CL)**
• LEISHMANIA MAJOR (CL)
• LEISHMANIA AETHIOPICA (CL)
• LEISHMANIA MEXICANA (COMPLEX) (CL)
• LEISHMANIA BRAZILLIENSIS (COMPLEX)(MCL)
• LEISHMANIA PERURIANA

8. MORPHOLOGY

9. LIFE CYCLE
• THE ORGANISM IS TRANSMITTED BY THE BITE OF SEVERAL SPECIES OF
BLOOD-FEEDING SAND FLIES (PHLEBOTOMUS) WHICH CARRIES THE
PROMASTIGOTE IN THE ANTERIOR GUT AND PHARYNX.
• IT GAINS ACCESS TO MONONUCLEAR PHAGOCYTES WHERE IT TRANSFORM
INTO AMASTIGOTES AND DIVIDES UNTIL THE INFECTED CELL RUPTURES.
THE RELEASED ORGANISMS INFECT OTHER CELLS.
• THE SANDFLY ACQUIRES THE ORGANISMS DURING THE BLOOD MEAL, THE
AMASTIGOTES TRANSFORM INTO FLAGELLATE PROMASTIGOTES AND
MULTIPLY IN THE GUT UNTIL THE ANTERIOR GUT AND PHARYNX ARE
PACKED.
• DOGS AND RODENTS ARE COMMON RESERVOIRS.

10. CUTANEOUS LEISHMANIASIS
`

12. VISCERAL LEISHMANIASIS
• VL (ALSO KNOWN AS KALA-AZAR, A HINDI TERM MEANING "BLACK FEVER")
• CAUSED BY L. DONOVANI COMPLEX-L. DONOVANI AND L. INFANTUM
• (THE LATTER DESIGNATED L. CHAGASI IN THE NEW WORLD)
• THESE SPECIES ARE RESPONSIBLE FOR ANTHROPONOTIC AND ZOONOTIC
TRANSMISSION

13. IMMUNOPATHOGENESIS
• MAJORITY OF INDIVIDUALS INFECTED BY L.DONOVANI OR L.INFANTUM
MOUNT A SUCCESSFUL IMMUNE RESPONSE AND CONTROL THE INFECTION,
NEVER DEVELOPING SYMPTOMATIC DISEASE.
• FORTY-EIGHT HOURS AFTER INTRADERMAL INJECTION OF KILLED
PROMASTIGOTES, THESE INDIVIDUALS EXHIBIT DELAYED-TYPE
HYPERSENSITIVITY TO LEISHMANIAL ANTIGENS IN THE LEISHMANIN SKIN
TEST (ALSO CALLED THE MONTENEGRO SKIN TEST).
• ACQUIRED RESISTANCE TO LEISHMANIAL INFECTION IS CONTROLLED BY
THE PRODUCTION OF INTERLEUKIN (IL) 12 ,INTERFERON (IFN) , TUMOR
NECROSIS FACTOR (TNF) , AND OTHER PROINFLAMMATORY CYTOKINES BY
THE T HELPER 1 (TH1) T LYMPHOCYTES.
• ORGANS OF THE RETICULOENDOTHELIAL SYSTEM ARE PREDOMINANTLY
AFFECTED, WITH REMARKABLE ENLARGEMENT OF THE SPLEEN, THE LIVER,
AND LYMPH NODES.
• THE TONSILS AND INTESTINAL SUBMUCOSA ARE ALSO HEAVILY
INFILTRATED WITH PARASITES. BONE MARROW DYSFUNCTION RESULTS IN
PANCYTOPENIA.

14. CLINICAL FEATURES
• INCUBATION PERIOD –FROM WEEKS TO MONTHS
• HIGH GRADE FEVER WITH CHILLS AND RIGOR
• SPLEEN BECOMES PALPABLE-REMARKABLY ENLARGED
• AT LATER STAGE-MILD HEPATOMEGALY
• WEIGHT LOSS AND CACHEXIA WITH HYPERPIGMENTATION INBROWN
SKINNED INDIVIDUALS
• PEDAL EDEMA WITH ASCITES-HYPOALBUMINEMIA
• BONE MARROW HYPERPLASIA WITH EVENTUAL BONE MARROW
DESTRUCTION-ANEMIA –SEVERE ENOUGH CAUSE CARDIAC FAILURE
• PANCYTOPENIA IS AN IMPORTANT FEATURE
• LEUCOPENIA-SECONDARY SKIN INFECTIONS LIKEMEASLES,PNEUMONIA,TB
BACILLARY OR AMEBIC DYSENTERY, GASTROENTERITIS
THROMBOCYTOPENIA- EPISTAXIS,RETINAL HEMORRHAGES,GI BLEED

15. SIR CHARLES DONOVAN
CHARLES DONOVAN ALSO
RECOGNIZED THESE SYMPTOMS IN
OTHER KALA-AZAR PATIENTS
AND PUBLISHED HIS DISCOVERY A
FEW WEEKS AFTER LEISHMAN. AFTER
EXAMINING THE PARASITE USING
LEISHMAN'S STAIN, THESE
AMASTIGOTES WERE KNOWN AS
LEISHMAN-DONOVANI BODIES

16. PROFILE VIEW OF A TEENAGE
BOY SUFFERING FROM
VISCERAL LEISHMANIASIS.
THE BOY EXHIBITS
SPLENOMEGALY, DISTENDED
ABDOMEN AND SEVERE
MUSCLE WASTING.

17. • Leishmania (Leishman- Donovan or
LD bodies). Lying in macrophage cells
from liver. Giemsa.

19. POST KALAAZAR DERMAL
LEISHMANIASIS
VL-PKDL=6M-3Y

20. • IN PKDL, PARASITES ARE SCANTY IN HYPOPIGMENTED MACULES BUT MAY BE
SEEN AND CULTURED MORE EASILY FROM NODULAR LESIONS.
• CELLULAR INFILTRATES ARE HEAVIER IN NODULES THAN IN MACULES.
LYMPHOCYTES ARE THE DOMINANT CELLS; NEXT MOST COMMON ARE
HISTIOCYTES AND PLASMA CELLS.
• IN ABOUT HALF OF CASES, EPITHELIOID CELLS—SCATTERED INDIVIDUALLY
OR FORMING COMPACT GRANULOMAS—ARE SEEN.
• THE DIAGNOSIS IS BASED ON HISTORY AND CLINICAL FINDINGS, BUT RK39
AND OTHER SEROLOGIC TESTS ARE POSITIVE IN MOST CASES.

21. LABORATORY DIAGNOSIS
• GOLD STANDARD DIAGNOSIS-DEMONSTRATION OF AMASTIGOTES IN TISSUE
ASPIRATES
• (P)-AMASTIGOTES (*) OF LEISHMANIA DONOVANI IN THE CELLS OF A SPLEEN.
• SMEARS –SPLENIC(95%)
• BM(60-85%)
• LN(50%)

22. • ELISA AND IFAT(INDIRECT
IMMUNOFLUORESCENT ANTIBODY)
• PCR OR LAMP(LOOP MEDIATED ISOTHERMAL
AMPLIFICATION)

23. BONE MARROW ASPIRATION

24. RK 39/28
PRINCIPLE-CHROMATOGRAPHY
RK 39 –RECOMBINANT AG,KINESIN
L.INFANTUM,39 AAS
RK 28-SUDAN(POSITIVE AFTER CURE –
YEARS)

25. CULTURE
NNN MEDIUM(NICOLLE MCNEAL
NAVY MEDIUM)

26. TREATMENT
TWO PENTAVALENT PREPARATIONS ARE AVAILABLE
• SODIUM STIBOGLUCONATE (100 MG OF SBV/ML)
• MEGLUMINE ANTIMONATE (85 MG OF SBV/ML).
• THE DAILY DOSE IS 20 MG/KG BY RAPID IV INFUSION OR IM INJECTION AND
THERAPY CONTINUES FOR 28–30 DAYS.
• ADVERSE REACTIONS TO SBVTREATMENT ARE COMMON AND INCLUDE
ARTHRALGIA, MYALGIA AND ELEVATED SERUM LEVELS OF
AMINOTRANSFERASES.
• ELECTROCARDIOGRAPHIC CHANGES SUCH AS PROLONGATION OF QTCTO
>0.5 S MAY HERALD VENTRICULAR ARRHYTHMIA AND SUDDEN DEATH.

27. AMPHOTERICIN B
• CONVENTIONAL AMB DEOXYCHOLATE IS ADMINISTERED IN DOSES OF 0.75–
1.0 MG/KG ON ALTERNATE DAYS FOR A TOTAL OF 15 INFUSIONS.
• FEVER WITH CHILLS IS AN ALMOST UNIVERSAL ADVERSE REACTION TO
AMB INFUSIONS. NAUSEA AND VOMITING ARE ALSO COMMON, AS IS
THROMBOPHLEBITIS IN THE INFUSED VEINS.
• ACUTE TOXICITIES CAN BE MINIMIZED BY ADMINISTRATION OF
ANTIHISTAMINES LIKE CHLORPHENIRAMINE AND ANTIPYRETIC AGENTS
LIKE ACETAMINOPHEN BEFORE EACH INFUSION.
• AMB CAN CAUSE RENAL DYSFUNCTION AND HYPOKALEMIA AND IN RARE
INSTANCES ELICITS HYPERSENSITIVITY REACTIONS, BONE MARROW
SUPPRESSION, AND MYOCARDITIS, ALL OF WHICH CAN BE FATAL.

28. • PAROMOMYCIN IS APPROVED IN INDIA FOR THE TREATMENT OF VL AT AN
IM DOSE OF 11 MG OF BASE/KG DAILY FOR 21 DAYS
• THIS REGIMEN PRODUCES A CURE RATE OF 95%
• MILTEFOSINE RECOMMENDED THERAPEUTIC REGIMENS FOR PATIENTS ON
THE INDIAN SUBCONTINENT ARE
• A DAILY DOSE OF 50 MG FOR 28 DAYS FOR PATIENTS WEIGHING <25 KG
• A TWICE-DAILY DOSE OF 50 MG FOR 28 DAYS FOR PATIENTS WEIGHING 25 KG
• 2.5 MG/KG FOR 28 DAYS FOR CHILDREN 2–11 YEARS OF AGE
• THESE REGIMENS RESULT IN A CURE RATE OF 94% IN INDIA.

29. PREVENTION
• VECTOR CONTROL
o INSECTICIDES,SPRAYS
o MOSQUITO NETS,CURTAINS
• RESERVOIR CONTROL
o DESTROYING STRAY DOGS
• VACCINATION