presentation about kalaazar in banga bandhu sheikh mujib medical university

1. SEMINAR
Dr. Amlendra Yadav
Dr. Shorna Rahman

2. Kala-azar

3. Definition
Kala-azar = black sickness , means visceral
leishmaniasis is a chronic infection of
reticuloendothelial system caused by
Leishmania donovani, transmitted by infected
female sandfly, Phlebotomas argentipes.

4. History
• Kala-azar ( kala- black , azar – fever ) , colour
of the skin of the patient become a strange
earthy-gray .
• It was first noted in India in 1880.
• Epidemics of the diseases have occured every
15-20 years .

5. Epidemiology
Kala-azar situation in World:
• It affects 88 countries of the world of which
72 are developing and 13 of then are
among the least developed countries.
• Five countries, namely India, Sudan,
Nepal, Bangladesh & Brazil account for
90% of the global cases

7. Kala-azar situation in Bangladesh:
• Kala-azar is one of the major public health problems
in Bangladesh and the disease is endemic for many
decades.
• During 1981-1985 only 8 Upazila reported kala-azar
• In 2004, 105 Upazilla.
• In 1993 case reported 397
• In 2005 case reported 8505
• In 2011 case reported 3376
Bangladesh has committed to eliminate kala-azar by
2015 (Incidence of kala-azar less than 1 case in
10,000 population at Upazila level).

8. District effected in Bangladesh
• Pabna
• Sirajgonj
• Dinajpur
• Rajsahi
• Mymensingh
• Natore
• Naogaon
• Tangail
• Gazipur
• Jamalpur
• Thakurgaon

10. Mode of transmission
• By bite of sandfly (phlebotomas argentipes)
• Blood transfusion
• Transplacental
• Organ transplantation
• Transmission by inoculation of culture of
L. Donovani

11. Agent
L. Donovani
Host
Children 5-15 years are affected most
Male are more commonly affected
Environment
Peak incidence 3 month after the onset of rains
Socio-economical condition
Primitive housing
Low standard of hygiene
Overcrowding

12. Vector
• The phlebotomize female sand fly .
• They are small, 1-4 mm, hairy flies, recognized by their
characteristic hoping movement & position of the wings which
are held nearly’ V’ shaped configuration .
• They sheldom rises above 0.5 m above ground
• Feeding mainly at night
• Seasonal variation – peak after the monsoon rains from August
– October

13. Morphological forms of L. Donovani

14. Life cycle of L. Donovani

15. Pathogenesis
• VL infections may heal spontaneously or may progress to chronic
disease .
• If spontaneous recovery occurs, the patient’s cell mediated
immunity (CMI) increases .
• If the individual is unable to mount an appropriate immune
response then the parasites disseminate in the Reticulo-endothelial
cells of the host.
• Alternatively the parasites may remain dormant and not present
itself until one’s immune system becomes compromised.
• Cellular immune mechanisms determines Resistance or
susceptibility to infection with Leishmania .

16. Pathogenesis continue….
• Resistance is mediatedd by interleukin 12 (IL-12) – driven
generation of a T helper 1 (Th1) cell response, with interferon-y
including classical macrophage activation and parasite killing .
• Susceptibility is associated with expansion of IL-4 producing Th-2
cells and/or the production of IL-10 and transforming growth
factor –B , which are the inhibotors of macrophage – mediated
parasite killing , and the generation of regulatory T cells and
alternatively activated macrophages .

17. Clinical feature
Incubation period: 2wks to 2years
Mean : 3-6months
Fever:
• Is the early symptom
• In early stage continuous or remittent in type
• In later stage become intermittent
• Fever usually 38-39º,but may 40-41

18. • Wasting-progressive, appetite unaltered with clean
moist tongue.
• Pallor-slowly progressive.
• Skin- dry, rough, earthy-gray colour.
• Hair-dry, brittle & tend to fall out.
• Oedema- in malnourished children.

19. • Splenomegaly-progressive.
• Hepatomegaly-enlarges to a lesser degree.
• Bleeding- epistaxis, purpuric patches,
petechiae, gum bleeding.
• Jaudice-in 10% cases.
• Diarrhoea
• Lymphadenopathy-usually not in indian kala-azor.

20. Differential diagnosis
• Malaria
• Milliary TB
• Leukemia
• Lymphoma
• Hemolytic anemia

21. Investigation
Indirect Evidence:
CBC-
• Hb low(5-8g/dl)
• TC-Progressive leukopenia(2000- 3000/cmm)
• DC-Neutropenia with relative lymphocytosis &
monocytosis
• PLT-low.
• PBF-Normocytic normochromic aneamia

22. Serological diagnosis by antibody detection
• Aldehyde test
• Direct agglutination test (DAT)
• Complement fixation test (CFT)
• Indirect Fluorescent Antibody test
• ELISA
• Immunochromatography (ICT)
- rK39

23. Serological diagnosis by antigen detection
• Latex agglutination test
DNA detection
• PCR

24. rK39
• Rapid dipstick test
• Based on the recombinant k39 protein

25. Test Sensitivity % Specificity %
Complement fixation
test
70-80 60-73
DAT 91-100 72-100
IFAT 55-70 70-89
ELISA (CSA) 80-100 50-70
ELISA ( rK39) 100 98
rK39 rapid strip test 100 88-98
Latex agglutination test 68-100 100

26. Direct evidence
• Demonstration of parasite in splenic, bone
marrow, lymph node aspirate or from
peripheral blood
• Culture of aspirate materials

27. LD bodies isolated by aspiration from different sites
Site sensitivity (%)
Spleen 95-98
Liver 75-85
Bone marrow 64-85
Lymph node 64

28. Clinical case definition for Kala-azar
• The diagnosis of Kala-azar will be based on the
following criteria in a symptomatic case:
-H/O fever for >2 wks
-Residing/travelling in endemic areas
-Any one of the following symptoms & signs:
• Splenomegaly
• Weight loss
• Anaemia
-And ‘rk39’test (+) positive .

29. Clinical case definition for PKDL
PKDL should be considered if all of the following
features are present
• Residing/travelling in endemic areas
• History of treatment of kala-azar any time in past
• Suggestive skin lesion without loss of sensation,
which may be macular, papular, nodular, or mixed
• Exclusion of other cause of skin disease
• ‘rk39’test (+) positive/ slit skin smear positive/ PCR
positive

30. Some definition

31. Primary Kala-azar(PKA)
An individual who is diagnosed to have KA with
above mentioned case definition and no history
of treatment for KA before will be considered as
primary Kala-azar.

32. Kala-azar treatment failure(KATF)
An individual who is diagnosed to have KA with
above mentioned case definition and history of
treatment for KA within last one year will be
reported as KATF. All efforts should be made to
diagnose RKA parasitologically by examination
of splenic smear or bone marrow or PCR

33. Relapse Kala-azar
An individual who is diagnosed to have KA with
above mentioned case definition and history of
treatment for KA any time in past but not within
last one year will be reported as RKA. All efforts
should be made to diagnose RKA
parasitologically by examination of splenic
smear or bone marrow or PCR

34. Post Kala-azar dermal leishmaniasis(PKDL)
An individual who is diagnosed to have PKDL
with above mentioned case definition will be
reported as PKDL

35. Management
• Supportive
• Drug Rx
• Control measures
• Follow up
• Prognosis

36. Supportive measures
• Maintenance of nutritional status
• Control of infection by proper antibiotics
• Blood transfusion if needed

37. Treatment
Primary Kala-azar(PKA)
1st line treatm1ensttline treatment
Drug of choice:
10 mg/kg iv over not less
Liposomal Amphoteracin B
than 2 hours
Single dose
Alternative choice:
Miltefosine
2.5 mg/Kg/Day in 2 divided
doses after meal PO
28days
(in case of missed dose- 35
days)
Paromomycin 15mg/kg/day im in gluteal
muscle( alternative buttock)
once a day
21 days

38. Miltefosine + paromomycin Miltefosine for 10 days
Paromomycin for 10 days
1st choice
LAmB+Miltefosine LAmB 5mg/kg iv on D1
Miltefosine 2.5mg/kg/day
from D2-D8
Alternate choice
LAmB+paromomycin LAmB 5mg/kg iv on D1
Paromomycin 15mg/kg/day
OD IM from D2-D11

39. Treatment
Primary Kala-azar(PKA)
1st line treatm2enndt line treatment
Amphoteracin B
deoxycholate
1mg/kg/day or alternate
day iv infusion in 5%
dextrose 500ml over 4-6
hours
15 doses
Sodiun stibogluconae(SSG) 20mg/kg/day IM OD 30 days

40. Treatment
KATF/RKA
• KATF & RKA cases will be treated with
alternative 1st line agent
• If alternative 1st line agent not available, then
a 2nd line agent should be used

41. Treatment
PKDL
1st line treatment
Miltefosine Adult:100mg/day BD
Children:2.5mg/kg/day BD
Not exceeding 50 mg/day
12 weeks
2nd line treatment
Amphotericin B
deoxcholate
1mg/kg/ day or alternate
day IV
15 doses per cycle with 6
cyles followed by 10 days
gap
SSG 20mg/kg/day IM 20 days, total 6 cycles
interval of 10 days in
between cycles

42. Target
The target of Kala-azor elemination is to reduce
the incidence of the disease to less than 1 case per
10,000 population at the upazilla level in Bangladesh by
the year 2015.

43. Complication
• Measles
• Pneumonia
• Bacillary dysentry
• TB
• Septicemia
• Epistaxis
• Severe malnutrition
• PKDL

44. Side effects of drugs
Drugs Side effects Safety monitering
LAmB Hypersensitivity, Fever,
Chills, hypotension
Renal impairment,
hypokalemia
Electrolyte, s. creatinine
Miltefosine Vomiting, diarrhoea,
hepatotoxicity,
nephrotoxicity
s. creatinine, s. ALT
Paramomycin Nephrotoxicity, ototoxicity s. creatinine

45. Prevention and control
Control of reservior
• Early detection of the cases and treatment.
Sandfly control
• Insecticide spraying (DDT) should be undertaken in
human dwellings, animal shelters.
• Spraying should be repeated at regular intervals to
reduce sand flies.
• Improvement of housing and general sanitation

46. Cont..
Personal prophylaxis
• The risk of infection can be reduced through
health education
• Avoiding sleeping on floor, using mosquito nets.
• Insect repellants

47. Follow up
Folow up done on 1st, 5th, 9th, 12th month after
completion of treatment
Clinical
fever, general well being, pallor, wt gain, spleen
size
Lab
TC, DC, platelet count, Hb

48. Criteria for cure
• Return of normal appetite
• Remission of fever
• Regression of spleen size
• Improvement in anemia and rise in
hemoglobin
• The full course of treatment has been taken
• Increase in body weight