Kala-azar

The leishmaniases are a group of diseases caused by protozoan parasites from more than 20 Leishmania species. These parasites are transmitted to humans by the bite of an infected female phlebotomine sandfly, a tiny 2-3 mm long insect vector. There are three main forms of the disease: cutaneous leishmaniasis (CL), visceral leishmaniasis (VL), also known as kala-azar, and mucocutaneous leishmaniasis (MCL). CL is the most common form, VL is the most severe form and MCL is the most disabling form of the disease.

In 2018, 92 and 83 countries or territories were considered endemic for, or had previously reported cases of, CL and VL, respectively.

Today, more than 1 billion people live in areas endemic for leishmaniasis and are at risk of infection. Globally, an estimated 30 000 new cases of VL and more than 1 million new cases of CL occur annually.

Visceral leishmaniasis (VL) also known as kala-azar (KA) is endemic in 75 countries across Asia, Africa and the Americas. India accounts for 18% of the global burden of kala-azar in 2020. Kala-azar remains a substantial public health problem in the country as it is present in 54 districts across four states — Bihar (33 out of 38 districts), Jharkhand (4 out of 24 districts), Uttar Pradesh (6 out of 75 districts) and West Bengal (11 out of 23 districts). Micro-stratification surveys reveal that there are 633 blocks in these four states that are endemic. Sporadic cases are also reported in other states including Assam, Gujarat, Himachal Pradesh, Jammu & Kashmir, Kerala, Madhya Pradesh, Haryana, Puducherry, Sikkim, Tamil Nadu and Uttaranchal.

Much progress has occurred in the country in the past decades. Kala-azar cases have decreased by 98% (1 275 cases in 2021) since the start of intensified activities in 1992 (77 102 cases). To get to the 2030 Sustainable Development Goals and WHO targets for kala-azar elimination as a public health problem, block level incidence of cases should be reduced to less than 1 case per 10 000 population. This target aligned with the new NTDs roadmap 2021-2030 (URL: https://www.who.int/publications/i/item/9789240010352). By the end of 2021, 98% of blocks have achieved the WHO elimination threshold  and only seven blocks which are yet to reach the targets. WHO is supporting the national programme in intensifying activities to help achieve targets and ensure sustainability of kala-azar elimination.

Post-kala-azar dermal leishmaniasis

A complication of kala-azar, is mainly seen in East Africa and South-East Asia, including India. It is characterized by discoloured (hypopigmented) flat skin (macular) rash, combined with some slightly elevated (maculopapular) or elevated (nodular) rash, usually in patients who have recovered from the disease. Post-kala-azar dermal leishmaniasis (PKDL) usually appears six months to one or more years after apparent cure of kala-azar, but it may occur earlier or even concurrently with kala-azar. PKDL heals spontaneously in most cases in Africa but rarely in patients in India.

Kala-azar-HIV co-infection

Kala-azar-HIV coinfected people have high chance of developing the full-blown clinical disease, and high relapse and mortality rates. Antiretroviral treatment reduces the development of the disease, delays relapses and increases the survival of the coinfected patients. As of 2021, leishmania-HIV coinfection has been reported from 45 countries. High Leishmania-HIV coinfection rates are reported from Brazil, Ethiopia and the state of Bihar in India.

Major risk factors

Socioeconomic conditions: Poverty increases the risk for kala-azar. Poor housing and domestic sanitary conditions (such as a lack of waste management or open sewerage) may increase sandfly breeding and resting sites, as well as their access to humans. Sandflies are attracted to crowded housing as these provide a good source of blood-meals. Human behaviour, such as sleeping outside or on the ground, may increase risk.

Malnutrition: Diets lacking protein-energy, iron, vitamin A and zinc increase the risk that an infection will progress to a full-blown disease.

Population mobility: Epidemics of both cutaneous and kala-azar are often associated with migration and the movement of non-immune people into areas with existing transmission cycles. Occupational exposure as well as widespread deforestation remain important factors.

Environmental changes
Kala-azar is climate-sensitive as it affects the epidemiology in several ways:

• changes in temperature, rainfall and humidity can have strong effects on vectors and reservoir hosts by altering their distribution and influencing their survival and population sizes;
• small fluctuations in temperature can have a profound effect on the developmental cycle of Leishmania promastigotes in sandflies, allowing transmission of the parasite in areas not previously endemic for the disease;
• drought, famine and flood can lead to massive displacement and migration of people to areas with transmission of kala-azar, and poor nutrition could compromise their immunity.

Symptoms

Kala-azar is characterized by irregular bouts of fever, substantial weight loss, swelling of the spleen and liver and severe anaemia. If the disease is not treated early and in time, affected individuals can die within two years.

Diagnosis and Treatment

• Diagnosis

  In Kala-azar, diagnosis is made by combining clinical signs with parasitological, or serological tests (such as rapid diagnostic tests). In cutaneous and mucocutaneous leishmaniasis serological tests have limited value and clinical manifestation with parasitological tests confirms the diagnosis. Anti-kala-azar treatment depends on the causative species and the condition of the patient (e.g. pregnancy, immunosuppression). Regardless of the causative Leishmania species, antileishmanial treatment cannot provide a complete cure. The parasite remains in the human body and can cause a relapse when there is immunosuppression.
  

• Treatment

Treatment is complex and should be administered by health personnel. Most antileishmanial medicines are injectable drugs. All patients diagnosed as with visceral leishmaniasis require prompt and complete treatment. Detailed information on treatment of the various forms of the disease by geographic location is available in the WHO technical report series 949, "Control of leishmaniasis". The first-line treatment for kala-azar in India is injectable liposomal amphotericin B 10mg/kg body weight and for PKDL, it is 12 weeks oral miltefosine adjusting the dosage according to age and weight of the patient.

Prevention and control

Prevention and control of kala-azar requires a combination of intervention strategies because transmission occurs in a complex biological system involving the human or animal reservoir host, parasite and sandfly vector. Key strategies for prevention are listed below:

• Early diagnosis and effective prompt treatment reduce the prevalence of the disease and prevents disabilities and death. It helps to reduce transmission and to monitor the spread and burden of disease. Currently there are highly effective and safe anti-leishmanial medicines particularly for kala-azar, although they can be difficult to use. Access to medicines has significantly improved thanks to a WHO-negotiated price scheme and a medicine donation programme through WHO.
• Vector control helps reduce or interrupt transmission of disease by decreasing the number of sandflies. Control methods include insecticide spray, use of insecticide-treated nets, environmental management and personal protection.
• Effective disease surveillance is important to promptly monitor and act during epidemics and situations with high case fatality rates under treatment.
• Social mobilisation and strengthening partnerships by mobilising and educating the community with effective behavioural change interventions must always be locally adapted. Partnership and collaboration with various stakeholders and other vector-borne disease control programmes is critical.

WHO response

WHO's work on leishmaniasis control involves:

• Supporting national kala-azar elimination programmes technically to produce updated guidelines and make disease control plans, including sustainable, effective surveillance systems, and epidemic preparedness and response systems.
• Monitoring disease trends and assessing the impact of control activities which will allow raising awareness and advocacy on the global burden of leishmaniasis and promoting equitable access to health services.
• Developing evidence-based policy strategies and standards for kala-azar elimination programme and monitoring their implementation.
• Strengthening collaboration and coordination among partners and stakeholders.
• Promoting research and use of effective leishmaniasis control including safe, effective and affordable medicines, as well as diagnostic tools and vaccines.
• Supporting national control programmes to ensure access to quality-assured medicines.