What is kala-azar?

Kala-azar is an Indian term (in Hindi and other regional languages in Ganges valley) as the disease as very common in India once and still occurs, which means black fever; kala (black) zar (fever). Contrary to the meaning of the name blackening or darkening of skin is uncommon (except in some parts of India). Kala-azar is visceral leishmaniasis (generally used for advanced and life threatening leishmaniasis.) which is a vector-borne disease, which covers broad spectrum of severity, as well as manifestations that can be chronic, subacute, or acute onset. Kala-azar is caused by Leishmania donovani (obligate intracellular protozoa).

How kala-azar is transmitted?

Kala-azar is transmitted from person-to-person by bite of female phlebotomine sandfly Phlebotomus argentipes and some other species. Kala-azar may also be transmitted by contamination of bite wound and if female sandfly is crushed on skin surface when feeding blood meal. There are also some reports of Kala-azar after blood transfusion.

Incubation period of kala-azar:

The incubation period of kala-azar is highly variable. Generally it varies from 1-4 months, but the range is from 10 days to 2 years. The extrinsic incubation period is 6-9 days, which is the time required inside the vector (female phlebotomine sandfly Phlebotomus argentipes) to become infective after an infective blood meal.

Global problem of kala-azar:

Several hundred thousand cases of Kala-azar and more than a million cases of cutaneous leishmaniasis occur every year throughout the world (mostly in the three regions mentioned below). Leishmaniasis is reported to be associated with the loss of approximately 2.4 million disability-adjusted life-years throughout the world. Kala-azar occurs throughout the world. But 90% of Kala-azar occurs in Bangladesh, India (Bihar State in Eastern India), Brazil and Africa (Sudan and adjoining countries). Other areas where Kala-azar can be seen are China, South America, Africa and the Mediterranean nations. The economics and environmental changes like unplanned urbanization, new industrial projects, large scale migration of can and man made environmental changes can increase the incidence of Kala-azar in an area. Kala-azar can also occur as coinfection with HIV/AIDS, which can lead o spread of Kala-azar in non endemic areas.

What are the clinical manifestations of kala-azar?

The most important clinical features of Kala-azar are fever, spleenomegally (enlargement of spleen), hepatomegally (enlargement of liver), weight loss and anemia. In endemic areas there may also be family history of Kala-azar. If darkening (as the meaning of the name kala-azar suggest) occurs, it generally occurs in hands, feet, abdomen and face.

PKDL (post kala-azar dermal leishmaniasis) may develop during or after therapy for Kala-azar, which is characterized by macules, papules, nodules, and patches mostly in the face. In Sudan PKDL is seen approximately half of the patients within 6 months of treatment for Kala-azar (visceral leishmaniasis), but heal spontaneously. But in India PKDL is seen less than 10% of patients treated for Kala-azar that may occur several years after treatment and usually require further treatment.

How to diagnose kala-azar?

There are several tests to diagnose Kala-azar like serological tests, demonstration of Leishmania, aldehyde test, Leishmanin test and supportive hematological tests. The only way to confirm the diagnosis of Kala-azar is demonstration of Leishmania in aspirates of bone marrow, spleen, liver or lymph nodes. After isolation of Leishmania the parasite should be cultured to confirm the identity of the Leishmania.

Among the serological tests ELISA (enzyme linked immunosrbent assay) is the most popular because it is a simple test to perform after collecting the whole blood in a filter paper and used for diagnosis as well as epidemiological studies. Other serological tests used for diagnosis of Kala-azar are Direct Agglutination test (DAT), Indirect Fluorescent Antibody test (IFAT), rk39 dipstick test etc.

Hematological findings of Kala-azar are progressive leucopenia, low hemoglobin, reverse albumin:globulin ratio, increased ESR (erythrocyte sedimentation rate) and increased IgG etc.

Leishmanin test:

Leishmanin test is also called Montenegro test based on skin reaction like tuberculin tests in tuberculosis. Standard and sterile preparations of Leishmanin (it is a preparation of 1 million promastigotes of leishmania per ml which are suspended in 0.5% phenol) are available commercially, 0.1 ml of which is injected intradermally on the flexor surface of forearm and examined after 48-72 hours for induration (raised and hardness of skin surface) and recorded. If induration is more than 5 mm in diameter, it is considered positive for Kala-azar. The test become positive usually 4-6 weeks after onset of cutaneous Leishmaniasis (CL), but is generally negative in active Kala-azar. But approximately 75% of patients of Kala-azar become positive within a year after recovery from Kala-azar. Leishmanin test is non specific and is not useful in diagnosis of Kala-azar, but is very useful in differentiating immune from non immune individuals (from Kala-azar) and is used in epidemiological studies to define population at risk of Kala-azar.

Aldehyde test:

Aldehyde test of Napier is used in countries like India for diagnosis of Kala-azar, although it is non specific test. In Aldehyde test 1-2 ml of serum (should be from venous blood) from Kala-azar patient is taken and 1-2 drops of 40% formalin is added to it. A test is considered positive if there is jellification (like boiled egg white) and light can not pass through it as it becomes opaque. The reaction should occur within 2-20 minutes to consider it strongly positive and any reaction occurring after 30 minutes is considered not significant. Aldehyde test of Napier becomes within 2-3 months after onset of Kala-azar and becomes negative within 6 months after cure. This is also non specific test and used in epidemiological studies for Kala-azar. Aldehyde test of Napier can also be positive in many other chronic diseases.

How Kala-azar is treated?

The treatment of choice of Kala-azar is pentavalent antimony compound sodium stibogluconate. The dose of sodium stibogluconate for treatment of Kala-azar is 20 mg/kg body weight once a day for 28 days given intravenously or intramuscularly. With 28 days treatment the relapse rate is very rare (0.05%) as compared to other regimens, which can be as high as 15%.

In the United States the CDC (Centers for Disease Control and Prevention) provides sodium stibogluconate to physicians licensed to practice in United States, through the CDC Drug Service (contact number 404-639-3670) under an IND mechanism with the FDA (Food and Drug Administration). In some parts of the world other antimony compound meglumine antimonite is also available. In some areas of the world generic antimony compounds are also available and the safety, quality and efficacy of these may vary.

Other drugs which are used in treatment of Kala-azar are the lipid formulations of amphotericin B which include liposomal amphotericin B and amphotericin B lipid complex (the FDA approved use of liposomal amphotericin B in Kala-azar at the dose of 3 mg/kg body weight per day on day 1-5, 14, and 21, a total of 21 mg/kg), Pentamidine isethionate (4 mg/kg thrice a week for total of 15-30 doses intravenously or intramuscularly), paromomycin sulfate (15–20 mg/kg once a day for approximately 21 days) and Miltefosine (oral preparation 2.5 mg/kg once a day for 4 weeks or 28 days).

All the patients treated with any of the above regimen should be examined 3 months to 1 year after treatment for possible relapse.

How to control & prevent kala-azar?

There is no effective vaccine available for Kala-azar, so the main preventive measure is aimed at control of reservoir of infection i.e. humans by early diagnosis and effective treatment with pentavalent antimony compound sodium stibogluconate, control of sandfly and maintenance of personal prophylaxis.

Control of reservoir of infection:

Man is the only known reservoir of Kala-azar in many endemic areas like India and early detection of cases and appropriate treatment of Kala-azar pentavalent antimony compound sodium stibogluconate may be sufficient to control Kala-azar. In highly endemic areas house-to-house surveys may be required for early detection of cases. In some areas there are animal reservoirs (dogs) and appropriate control measures should be undertaken and control of dogs and rodents have given good results in such areas with reduced number of cases of Kala-azar.

Control of sandflies:

This is another effective measure in controlling Kala-azar and other leishmaniasis. Control of sandfly can be achieved by insecticide spray (in many places DDT is used but becoming resistant, but in many countries DDT is banned), elimination of breeding places of sandflies like cracks in mud or stone walls, keeping the surrounding areas of house (from firewood, bricks, rubbish etc.), locating poultry and cattle sheds far from human dwellings and improvement of general sanitation and housing.

Personal prophylaxis:

By taking personal prophylaxis it is possible to reduce the risk of infection of Kala-azar. Use of protective fine mesh nets around bed, avoidance of sleeping on the floor etc. can help in reducing the risk of infection. Insect repellents in the form of creams, lotions, or sticks can reduce the rate and risk of infection. For long lasting effects keeping the surrounding environment clean is the best method. There are no drugs available for personal prophylaxis against Kala-azar.