KALA-AZAR

Leishmaniasis denotes varied presentations of infection with multiple species of an intracellular parasite— Leishmania; while the term kala-azar refers to typical manifestations of visceral leishmaniasis, i.e.

In India, leishmaniasis is still seen in four states: Bihar, Uttar Pradesh, Jharkhand and West Bengal, though number of cases have declined by over 98% in last decade and India aims to eliminate Kala-azar by 2023.

Epidemiology: Indian kala-azar is mainly caused by L. donovani, which is dimorphic in life cycle—aflagellate promastigote form in the vector and an aflagellate amastigote form in macrophages of human host.

Reservoir of infection is an infected human host, harboring amastigote forms within reticuloendothelial system and, intermittently in peripheral smear.

Mode of transmission is vector-borne, by a female sandfly—phlebotomus, which breeds in the hot-humid climate and gets infected after biting infected humans. In the vector, parasite assumes a promastigote form (leptomonads) to proliferate in gut and then ascends to pharynx during next 6-9 days (extrinsic incubation period).

Pathogenesis: After infected bite, parasite enters into macrophages to transform in amastigote form (Leishmania bodies or LD bodies) and replicates intra­cellularly. These infected macrophages eventually concentrate in spleen, liver and bone marrow, leading to hyperplasia of reticuloendothelial system-pathological hallmark of disease. Rarely, congenital and blood-borne transmission have been reported.

Clinical spectrum depend on the susceptibility and nutrition of the host as well as virulence and size of inoculums:

• Sub-clinical infection is more common than clinical disease, identified by a delayed hypersensitivity response to leishmania antigens (Montenegro skin test)

• Visceral leishmaniasis (kala-azar), is the commonest manifestation in children (Fig.

Typical double-rise fever of kala-azar is uncommon in children. Long-standing cases may develop signs of hypersplenism, i.e. severe anemia, bleeding tendency and recurrent infections, as well as signs of hepatocellular failure, e.g. jaundice, edema and ascites. Untreated cases are usually fatal.

• Post kala-azar dermal leishmaniasis is rare in childhood, seen after many years of treatment and cure of visceral disease with development of multiple hypopigmented, erythematous or nodular lesions over face, back and extensor aspect of extremities, which persist for many years before disappearance.

Fig. 10.19: Kala-azar: Clinical (cachexia with splenomegaly).

• Rare presentations, uncommon in India, include localized or diffuse cutaneous leishmaniasis (Oriental sore) or mucosal leishmaniasis.

Kala-azar in HIV-infected population is an opportunistic infection, presenting as reactivation of old infection with prominent GIT involvement, without significant splenohepatomegaly.

Diagnosis depends on:

• Clinical tetrad of gross splenomegaly, anemia, failure to thrive and skin pigmentation, with/without fever, in a case from endemic region.

• Rapid diagnostic kits based on the antibody immuno­assay with gt;90% sensitivity and specificity

• Demonstration of LD bodies, in splenic aspirate (gt;95%) or bone marrow aspirate (60-70%) (Fig. 10.20).

• Parasitic culture from above samples on Novy- McNeal-Nicolle (NNN) media, are less sensitive but allow detection of promastigote form and species identification for epidemiological studies.

• Serological tests, e.g.

• Other laboratory abnormalities include moderate anemia, leukopenia, thrombocytopenia and hyper­gammaglobulinemia (gt; 5 gm/dl).

Aldehyde test (Napier test) is a screening test, based on development of hypergammaglobulinemia in kala-azar. Add 1-2 drops of formalin in 1 ml of patient's serum. Milky-white opacification within 30 minutes indicates positive result. Test is positive after 2-3 months of the onset of illness and turns negative by 6 months of cure.

Leishmanin test-an intradermal test to assess cutaneous reaction to a promastigote suspension (leishmanin),

Fig. 10.20: Kala-azar: LD bodies (amastigote form of L. donovani).

is of no use for diagnosis of active kala-azar, but helps to distinguish immune (gt;5 mm induration) from non- immune subjects for epidemiological studies.

Management of kala-azar aims to achieve clinical and parasitic cure, as well as to prevent relapses, by specific therapy and supportive measures, e.g. correction of anemia, undernutrition and intercurrent infections.

According to operational guidelines for elimination of kala- azar in India 2015, based on WHO recommendation, current treatment guidelines are as follows:

• Single-dose Liposomal Amphotericin (IV 10 mg/kg, infused over 2 hours) is the treatment of choice for all ages, including children.

• PO Miltefosine (2.5 mg/kg/d OD) for 28 days is an equally effective option with oral convenience, but should not be used in children lt;2 years, pregnant and lactating women and cases with Co-HIV infection.

• Amphotericin B deoxycholate (IV 1 mg/kg/dose over 8 hrs x 15 doses) may be used in refractory cases.

• Combination of Miltefosine (PO 2.5 mg/kg/d OD) with Paromomycin (IM 11 mg/kg/dose OD) for 10 days may be used, if IV liposomal amphotericin infusion is not possible.

Other drugs, e.g. sodium stibogluconate, pentamidine, etc. are no longer recommended due to treatment failures and toxicity. Oral therapy with ketoconazole or allopurinol is effective in cutaneous leishmaniasis but has no role in kala-azar.

Splenectomy is indicated only in cases with massive splenomegaly on the verge of rupture or associated hypersplenism.

All treated cases should be reassessed with splenic/ marrow aspirate after 3 months to exclude late relapse, which should be treated as a fresh case.

Prevention of kala-azar depends on: (a) controlling the source, i.e. identification and adequate therapy of infected cases, (b) controlling the vector by residual insecticide sprays and sanitation measures, and (c) personal prophylaxis against mosquito bite by repellents and nets.

National Kala-azar Elimination Programme (2010) aims to reduce the annual incidence to lt; 1/10000 population at block PHC level in endemic districts and is being implemented under NVBDCP involving: (a) early diagnosis and complete case management, (b) integrated vector management and vector surveillance, (c) supervision, monitoring, surveillance and evaluation, and (d) IEC activities, with inter-sectoral convergence.

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