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SEMINAR 
Dr. Amlendra Yadav 
Dr. Shorna Rahman
Kala-azar
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.
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 .
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
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).
District effected in Bangladesh 
• Pabna 
• Sirajgonj 
• Dinajpur 
• Rajsahi 
• Mymensingh 
• Natore 
• Naogaon 
• Tangail 
• Gazipur 
• Jamalpur 
• Thakurgaon
Mode of transmission 
• By bite of sandfly (phlebotomas argentipes) 
• Blood transfusion 
• Transplacental 
• Organ transplantation 
• Transmission by inoculation of culture of 
L. Donovani
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
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
Morphological forms of L. Donovani
Life cycle of L. Donovani
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 .
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 .
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
• 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.
• 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.
Differential diagnosis 
• Malaria 
• Milliary TB 
• Leukemia 
• Lymphoma 
• Hemolytic anemia
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
Serological diagnosis by antibody detection 
• Aldehyde test 
• Direct agglutination test (DAT) 
• Complement fixation test (CFT) 
• Indirect Fluorescent Antibody test 
• ELISA 
• Immunochromatography (ICT) 
- rK39
Serological diagnosis by antigen detection 
• Latex agglutination test 
DNA detection 
• PCR
rK39 
• Rapid dipstick test 
• Based on the recombinant k39 protein
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
Direct evidence 
• Demonstration of parasite in splenic, bone 
marrow, lymph node aspirate or from 
peripheral blood 
• Culture of aspirate materials
LD bodies isolated by aspiration from different sites 
Site sensitivity (%) 
Spleen 95-98 
Liver 75-85 
Bone marrow 64-85 
Lymph node 64
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 .
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
Some definition
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.
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
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
Post Kala-azar dermal leishmaniasis(PKDL) 
An individual who is diagnosed to have PKDL 
with above mentioned case definition will be 
reported as PKDL
Management 
• Supportive 
• Drug Rx 
• Control measures 
• Follow up 
• Prognosis
Supportive measures 
• Maintenance of nutritional status 
• Control of infection by proper antibiotics 
• Blood transfusion if needed
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
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
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
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
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
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.
Complication 
• Measles 
• Pneumonia 
• Bacillary dysentry 
• TB 
• Septicemia 
• Epistaxis 
• Severe malnutrition 
• PKDL
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
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
Cont.. 
Personal prophylaxis 
• The risk of infection can be reduced through 
health education 
• Avoiding sleeping on floor, using mosquito nets. 
• Insect repellants
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
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
About Kala azar in bangladesh

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About Kala azar in bangladesh

  • 1. SEMINAR Dr. Amlendra Yadav Dr. Shorna Rahman
  • 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
  • 6.
  • 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
  • 9.
  • 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
  • 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