• Kala-azar is a vector borne disease
• Sandfly of genus Phlebotomus argentipes are the only known vectors of kala-azar in India
• Indian Kala-azar has a unique epidemiological feature of being Anthroponotic; human is the only known reservoir of infection
• Female snadflies pick up parasite (Amastigote or LD bodies)while feeding on an infected human host.
• Parasite undergo morphological change to become flagellate (Promastigote or Leptomonad), development and multiplication in the gut of sandflies and move to mouthparts
• Healthy human hosts get infection when an infective sandfly vector bites them

Kala-azar Vector in India

• There is only one sandfly vector of Kala-azar in India Phlebotomus aregentipes

• Sandflies are small insects, about one fourth of a mosquito.  The length of a snadfly body ranges from 1.5 to 3.5 mm.
• Adult is a small fuzzy, delicately proportionate fly with erect large wings. The entire body including wings is heavily clothed with long hairs.
• Life cycle consists of egg, four instars of larvae, pupa and adult. The whole cycle takes more than a month, however, duration depends on temperature and other ecological conditions
• They prefer high relative humidity, warm temperature, high subsoil water and abundance of vegetation.
• Sandflies breed in favourable micro-climatic conditions in places with high organic matter that serve as food for larvae
• These are ecologically sensitive insects, fragile and cannot withstand desiccation

How Kala-azar is Diagnosed?

• Clinical:
  • A case of fever of more than 2 weeks duration not responding to antimalarials and antibiotics. Clinical laboratory findings may include anaemia, progressive leucopenia thrombocytopenia and hypergammaglobulinemia

• Laboratory: 
  • Serology tests: Variety of tests are available for diagnosis of Kala-azar. The most commonly used tests based on relative sensitivity; specificity and operationally feasibility include Direct Agglutination Test (DAT), rk39 dipstick and ELISA. However all these tests detect IgG antibodies that are relatively long lasting. Aldehyde Test is commonly used but it is a non-specific test. IgM detecting tests are under development and not available for field use.
  • Parasite demonstration in bone marrow/spleen/lymphnode aspiration or in culture medium is the confirmatory diagnosis. However, sensitivity varies with the organ selected for aspiration. Though spleen aspiration has the highest sensitivity and specificity (considered gold standard) but a skilled professional with appropriate precaustions can perform it only at a good hospital facility.

• Differential Diagnosis:

• Typhoid

•  Miliary tuberculosis

• Malaria  

• Brucellosis

• Amoebic liver abscess 

• Infectious mononucleosis

• Lymphoma, Leukemia

• Tropical splenomegaly

• Portal hypertension

What is the Treatment of Kala-azar?

• Kala-azar Drugs available in India

• Sodium Stibogluconate (indigenous manufacture, registered for use & sale)

• Pentamidine Isethionate: (imported, registered for use)
• Amphotericin B: (indigenous manufacture, registered for use and sale)
• Liposomal Amphotericin B: (indigenous manufacture & import, registered for use and sale)
• Miltefosine (imported/ registered for use & sale)
• Drug Policy under Kala-azar Elimination Programme as per recommendations of Expert Committee (2000) – (This drug policy is under review)

• First Line Drugs

      A.  Short Term

• Areas with SSG sensitivity >90%

                    -  SSG IM/IV 20mg/kg/day X 30 days

• Areas with SSG sensitivity <90%

                    -  Amphotericin B 1mg/kg b.w. IV infusion daily or alternate day for 15-20 infusions. Dose can be increased

                        in patients with incomplete response with 30 injections

      B.  Long Term

• Areas with high level of SSG resistance (>20%)

                   -   Miltefosine 100 mg daily x 4 weeks (after phase III studies completed with proven safety & efficacy)

• Areas with SSG sensitivity >80%

                   -   SSG IM/IV 20mg/kg/day X 30 days

                   -   Miltefosine 100 mg daily x 4 weeks (after phase III studies completed with proven safety & efficacy)

• Second Line Drugs

      A. SSG Failures

                  -   Amphotericin B 1mg/kg b.w. IV infusion daily or alternate day for 15-20 infusions. Dose can be increased in patients

                      with incomplete response with 30 injections

     B.  SSG and Miltefosine Failures

                        -    Liposomal Amphotericin B (when final results are available with proven efficacy and safety)

Treatment of PKDL

•  SSG in usual dosages for KA could be given up to 120 days

• Repeated 3-4 courses of Amphotericin B can be given in patients failing SSG treatment

What is the extent of problem of Kala-azar in India? 

• Endemic in eastern States of India namely Bihar, Jharkhand, Uttar Pradesh and West Bengal
• 48 districts endemic; sporadic cases reported from a few other districts
• Estimated 165.4 million population at risk in 4 states
• Mostly poor socio-economic groups of population primarily living in rural areas are affected

Kala-azar Control Efforts in India 

• An organized centrally sponsored Control Programme launched in endemic areas in 1990-91
• Government of India provided kala-azar medicines, insecticides and technical support and the State governments implemented the programme through primary health care system and district/zonal and State malaria control organizations and provided other costs involved in strategy implementation

• Programme strategy included:

      -    Vector control through IRS with DDT up to 6 feet height from the ground twice annually

      -   Early Diagnosis and Complete treatment

      -   Information Education Communication

     -   Capacity Building

• Programme intensified in 1991-92 which led to improved case registration through primary health care system
• Programme Achievemnets

     –   Within 3 years of intensification (1995 as compared to 1992)

•  70.66% decline in annual incidence

•  80.48% decline in deaths

      -   By 2003 as compared to 1992

• 76.38% decline in incidence

• 85.20% decline in deaths

KALA-AZAR SITUATION IN INDIA SINCE 2002