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Leishmaniasis: a Neglected Tropical Disease Direct Research Journal of Health and Pharmacology Vol.6 (3), pp. 27-34, August 2018 ISSN 2449-0814 DOI: https://doi.org/10.5281/zenodo.3374950 Article Number: DRJHP37502183 Copyright © 2018 Author(s) retain the copyright of this article https://directresearchpublisher.org/drjhp/ Review Leishmaniasis: A neglected tropical disease *1Makun Babazhitsu, and 2Awosanya Joseph Abioye 1Department of Medical Microbiology and Parasitology, Faculty of Basic Clinical Sciences, College of Health Sciences, Usmanu Danfodiyo University, Sokoto, Sokoto State, Nigeria. 2Department of Medical Microbiology and Parasitology, Ekiti state University, Ado-Ekiti, Ekiti state, Nigeria. *Corresponding Author E-mail: [email protected] Received 30 June 2018; Accepted 20 July, 2018 Leishmaniasis refers to a diverse spectrum of clinical knowledge of clinical symptoms, diagnostic possibilities, syndromes caused by infection with protozoan parasites of and available treatment options. This article highlights the the genus Leishmania . They are widely distributed across biology, life cycle, diagnostic, chemotherapeutic, and the tropical, subtropical, and temperate regions in 88 strategies to control Leishmaniasis. countries, 72 of which are in developing areas of the world. The diagnosis and treatment of the different syndromes produced by these parasites are particularly difficult in Keywords: Leishmaniasis; biology; life cycle; diagnosis; developed and non-endemic countries because of poor treatment; prevention INTRODUCTION Leishmaniasis is a neglected vector-borne tropical calculated to be as high as 0.2–0.4 million people per infection that is considered to be a disease of the poor year, approximately 90% of all these are found in three (WHO, 2014). It is widely distributed across the tropical, areas: the drainage basin of the Ganges river in eastern subtropical, and temperate regions; extending from china India and neighboring areas of southern Nepal (Terai) across Asia, India, the Arabian Peninsula, the Middle and areas of Bangladesh that share the same ecology; East, the Mediterranean basin, East and West Africa and the Sudan, where a large epidemic has occurred among South America (Pace,2014). Three hundred fifty million displaced people (Alvar et al ., 2012). women, men, and children are at risk in widely scattered Cutaneous leishmaniasis (CL) has been considered by areas, with 14 million people directly affected by the the World Health Organization (WHO) a category 1 disease (Pace, 2014). Based on the pattern of organ emerging and uncontrolled disease (De Vries et al ., pathology, leishmaniasis is sub-divided into three clinical 2015), approximately 90% of the world’s CL cases occur types, namely visceral (kala-azar), the most important in Iran, Saudi Arabia, and Syria in the Middle East; in disease; cutaneous, the most common; and muco- Afghanistan in Central Asia; and in Brazil and Peru in cutaneous. Among parasitic diseases, mortality from Latin America (Desjeux, 2004). Approximately 35,000 leishmaniasis is second only to malaria and, in terms of cases of mucosal leishmaniasis occur annually, mainly in disability-adjusted life years (DALYs), the third-most Brazil, Peru, and Bolivia (Pace, 2014). VL is hypo common cause of morbidity after malaria and endemic in Mediterranean countries; cases in this area schistosomiasis, with children under 15 years of age account for 5–6% of the global burden (Daniella, 2015). It suffering most of the disease burden (Daniella, 2015). does not necessarily lead to clinical disease; most The number of cases of visceral leishmaniasis (VL) is infections remain asymptomatic, but malnutrition and Official Publication of Direct Research Journal of Health and Pharmacology: Vol.6 (3), August 2018, ISSN 2449-0814 Direct Res. J. Health Pharm. 28 immune suppression, notably HIV, predispose to clinical causing cell rupture and release into the circulation. diseases (Okwor and Uzonna, 2013). VL has also Amastigotes are carried out in the circulation to various emerged as an important opportunistic disease in organs like liver, spleen and bone marrow and invade the persons with acquired immunodeficiency syndrome reticuloendothelial cells like macrophages and endothelial (AIDS) in the Mediterranean region, mainly in France, cells (Apurba et al ., 2014). Italy, Portugal, and Spain (Monge-Maillo et al ., 2014). Since highly active antiretroviral therapy was introduced SANDFLY in 1997, a marked decrease in the number of co-infected cases both in these regions and in India have been During the blood meal taken up by the sandfly, the reported (Singh, 2014). Persons who have had organ amastigotes are ingested and transformed into transplants, and in association with other conditions in promastigote forms in the insect midgut. Promastigotes which cell-mediated immunity is compromised, VL multiply by longitudinal fission and pass through various presents as opportunistic disease. In a multicenter study stagessuch as: by Clemente, it was observed that diagnosis was frequently delayed and relapses were common after Amastigote → procyclic promastigote → nectomonad treatment (Clemente et al ., 2015). This disease remains a promastigote → haptomonad promastigote →leptomonad major neglected tropical disease, and a strategic promastigote → metacyclic promastigote (Apurba and framework for its control in the WHO European region Sandhya, 2014). The metacyclic promastigotes multiply has been applied (World Health Organization, Regional in the midgut of vector by binary fission and a small Office for Europe, 2014). proportion migratesto the foregut (proboscis). They infect a new host during another blood meal. The duration of the life cycle in sandfly varies from 4 to 18 days LIFE CYCLE depending on the specie (Apurba and Sandhya, 2014) (Figure 1). Depending on the Leishmania sp., the sandfly These intracellular protozoa have a complex digenetic life genus, and the geographic location, the major reservoirs cycle, requiring a susceptible vertebrate host and a are canines, rodents, or humans (Andrade et al ., 2007; permissive insect vector, which allow their transmission. Bates, 2007). Although most transmission is by sandfly Female sand flies of the genus Lutzomyia in the bites, Leishmania can be transmitted by blood Americas and Phlebotomus elsewhere transmit transfusions, sharing of needles by intravenous drug Leishmania spp. (Lewis, 1987). The sand flies are abusers, occupational exposures, congenital modified pool feeders, meaning that they feed on pooled transmission, and rarely by sexual transmission (Dey and blood from their bite. Adults, males and females, are Singh, 2006). Leukodepletion effectively reduces or recognized by their small size, hairy body, the wings held eliminates transfusion-associated risk of Leishmania erect on the body when resting, and a bouncy flight. infection (Cruz et al ., 2002). Females are blood feeders and, in general, tend to bite at night or in twilight, but also can sting during the day in CLASSIFICATION OF LEISHMANIASIS forested areas (Brazil et al ., 2015). Leishmania has two subgenera L. Leishmania and L. Viannia. The main difference between the twosubgenera MODE OF TRANSMISSION is that promastigotes of the subgenus Viannia develop in the midgut andhindgut of sandfly where as that of Bite of an infected sandfly mainly during the late evening subgenus Leishmania develop in the anterior portionof or the night time. Minimum 10–1,000 promastigotes per the alimentary tract of sandfly. Both of the subgenera infective bite are required to initiate the infection (Apurba comprise of nearly 20 specie (Abazid et al ., 2012); Old et al ., 2014). world leishmaniasis: Affects Asia, Africa and Europe and transmitted by sandfly (Genus Phlebotomus ) New World Leishmaniasis : Affects Central and South America and transmitted by sandfly (Genus Lutzomyia ) (Tables 1-3). VERTEBRATE HOSTS, INCLUDING HUMANS CLINICAL SYNDROMES OF LEISHMANIASIS Promastigotes are regurgitated from the midgut rarely or INCLUDE directly discharged from foregut (proboscis) of the female sandfly into the skin of the vertebrate host. Promastigotes Visceral leishmaniasis (VL) are phagocytosed by the skin macrophages and Post–kala-azar dermal leishmaniasis (PKDL) transform into amastigote forms within 12–24 h. The Cutaneous leishmaniasis (CL) amastigote forms inside the macrophages multiply further Diffuse cutaneous leishmaniasis (DCL) Official Publication of Direct Research Journal of Health and Pharmacology: Vol.6 (3), August 2018, ISSN 2449-0814 Babazhitsu and Awosanya 29 Figure 1. Sandfly mode of transmission of leishmaniasis. Leishmaniasis recidivans (LR) Mucocutaneous leishmaniasis (MCL) infection to VL cases are reported to range from 6.5: 1 in children to 18: 1 in adults with L. infantum/L. chagasi in northeastern Brazil (Evans et al ., 1992). The incubation VISCERAL LEISHMANIASIS (VL) period for full-blown visceral leishmaniasis is typically 3- 8 months, Persons who are immunocompromisedby AIDS, Visceral leishmaniasis is mainly caused by the L. neoplasm, or immunosuppressive therapy are at donovani and sometimes by L. infantum, (designated as increased risk of asymptomatic parasitemia (Orsini et al ., L. chagasi in the New World) together known as L. 2012) and developing progressive disease. Classic donovani complex (Kuhls et al ., 2011). VL is a spectrum visceral leishmaniasis, or kala-azar, is characterized by of symptoms and findings. At one extreme are persons fever, malaise, weight loss, hepatomegaly, and with asymptomatic, in
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