KALA

Visceral leishmaniasis (kala-azar) is a worldwide disseminated protozoal infection primarily transmitted by sand flies. Because host defense against this intracellular infection is T-cell-dependent, kala-azar has predictably joined the list of AIDS-related opportunistic infections in endemic areas. The vast majority of patients with AIDS-associated kala-azar are currently found in southern Europe (the Mediterranean basin, especially Spain in injection drug users); future cases will inevitably arise in other endemic regions including India, East Africa and Sudan, and Brazil. In CD4 cell-deficient HIV-infected individuals, kala-azar likely represents recrudescence of previously controlled asymptomatic infection; in drug users, newly acquired infection may result from transmission via shared needles. Coinfected patients are frequently parasitemic and may show atypical clinical presentations, unusual multi-organ involvement, and absent antileishmanial antibodies. Diagnosis is made by microscopic examination or culture of aspirate or biopsy of any involved tissue (primarily bone marrow) or by blood smear or culture. Conventional treatment (pentavalent antimonials) induces initial remission in about 50% of patients; amphotericin B and its new lipid formulations appear more active. If suppressive maintenance therapy is not used, relapse within 1 year is typical. In AIDS patients with a first episode of visceral kala-azar, up to 25% die within 1 month if treatment is stopped. Optimal primary and secondary prophylaxis for AIDS-related kala-azar remain to be determined; life-long maintenance therapy is becoming an accepted approach.

Post-kala-azar dermal leishmaniasis (PKDL) is a cutaneous sequel of visceral leishmaniasis (VL) or kala-azar and has become an entity of epidemiological significance by virtue of its ability to maintain the disease in circulation during inter-epidemic periods. PKDL has been identified as one of the epidemiological marker of "kala-azar elimination programme." Data obtained in 2018 showed PKDL distribution primarily concentrated in 6 countries, which includes India, Sudan, south Sudan, Bangladesh, Ethiopia, and Nepal in decreasing order of case-burden. In India, PKDL cases are mainly found in 54 districts, of which 33 are in Bihar, 11 in West Bengal, 4 in Jharkhand, and 6 in Uttar Pradesh. In West Bengal the districts reporting cases of PKDL cases include Darjeeling, Uttar Dinajpur, Dakshin Dinajpur, Malda, and Murshidabad. The vulnerability on the young age is documented in various studies. The studies also highlights a male predominance of the disease but recent active surveillance suggested that macular form of PKDL shows female-predominance. It is recommended that along with passive case detection, active survey helps in early identification of cases, thus reducing disease transmission in the community. The Accelerated plan for Kala-azar elimination in 2017 introduced by Government of India with the goal to eliminate Kala-azar as a public health problem, targets to reduceing annual incidence <1/10,000. Leishmania donovani is the established causative agent, but others like L. tropica or L. infantum may occasionally lead to the disease, especially with HIV-co-infection. Dermal tropism of the parasite has been attributed to overexpression of parasite surface receptors (like gp 63, gp46). Various host factors are also identified to contribute to the development of the disease, including high pretreatment IL 10 and parasite level, inadequate dose and duration of treatment, malnutrition, immuno-suppression, decreased interferon-gamma receptor 1 gene, etc. PKDL is mostly concentrated in the plains below an altitude of 600 mts which is attributed to the environment conducive for the vector sand fly (Phlebotumus). Risk factors are also linked to the habitat of the sand fly. Keeping these things in mind "Integrated vector control" is adopted under National vector borne disease control programme as one of the strategies to bring down the disease burden.

Post-kala-azar dermal leishmaniasis (PKDL) follows visceral leishmaniasis (VL, kala-azar) in 10-60% of cases. It is characterized by an asymptomatic skin rash, usually starting in the face and consisting of macules, papules, or nodules. Diagnosis is difficult in the field and is often made clinically. There is an extensive differential diagnosis, and parasitological confirmation is preferred particularly when drug treatment is considered. The response to treatment is difficult to assess as this may be slow and lesions take long to heal, thus possibly exposing patients unnecessarily to prolonged drug treatment. Biomarkers are needed; these may be parasitological (from microscopy, PCR), serological (from blood, or from the lesion), immunological (from blood, tissue), pathological (from cytology in a smear, histology in a biopsy), repeated clinical assessment (grading, photography), or combinations. In this paper, we will review evidence for currently used biomarkers and discuss promising developments.