About Kala azar in bangladesh

SEMINAR

Dr. Amlendra YadavDr. 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-azarAn 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 treatment 1st line treatmentDrug of choice:Liposomal Amphoteracin B

10 mg/kg iv over not less 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 daysParomomycin for 10 days

1st choice

LAmB+Miltefosine LAmB 5mg/kg iv on D1Miltefosine 2.5mg/kg/day from D2-D8

Alternate choice

LAmB+paromomycin LAmB 5mg/kg iv on D1Paromomycin 15mg/kg/day OD IM from D2-D11

Treatment Primary Kala-azar(PKA)

1st line treatment 2nd 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

TreatmentPKDL

1st line treatment

Miltefosine Adult:100mg/day BDChildren:2.5mg/kg/day BDNot 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 drugsDrugs Side effects Safety monitering

LAmB Hypersensitivity, Fever, Chills, hypotensionRenal 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 treatmentClinical fever, general well being, pallor, wt gain, spleen sizeLabTC, 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