مستخدم:Mays issa/ملعب
Leishmaniasis is a group of disease caused by the intrace
Leishmaniasis is a multifarious vector-borne neglected tropical disease (NTD) varying in the form of disease onset and includes cutaneous (CL), muco-cutaneous (MCL), visceral (VL), and post kala-azar dermal leishmaniasis (PKDL) caused by at least 20 species of the obligate intracellular parasite, Leishmania [1]. Of these, VL is the most severe form affecting visceral organs like spleen and liver and can prove fatal if left untreated[2].CL and MCL forms are comparatively less severe, with the former manifesting self-healing ulcers and the latter resulting in disfiguring lesions of oro-pharyngeal mucosal linings. The disease is transmitted by female Phlebotomine sp[3]. and Lutzomyia sp. sand flies. However, transmission of the disease is rare by syringe sharing, blood transfusions, or from mother to foetus[3].The World Health Organisation (WHO) enlists leishmaniasis as the second most severe NTD next to malaria and estimates over a million fresh cases annually [4]. The existence of leishmaniasis can be dated back to as early 2500–1500 B.C[5]. based on archaeological indications including pictures, mummified bodies, and statues (Elisama et al, 2014). The detailed description of CL (termed as “Apello Boil”) was given by Alexander Russel. In 1903 Sir William Leishman and Charles Donovan provided the clinical description of VL (termed as “Kala-azar”) [5]..
Currently, the disease is prevalent in tropical and sub-tropical countries and southern Europe and covers a geographic range of approximately 90 countries. According to WHO reports, apart from Australia and Antarctica, the disease can be found in people of every continent. In the Old World, leishmaniasis is reported in some parts of Asia, the tropical regions and northern part of Africa, southern Europe, and Middle East. In the New World, it is prevalent in some areas of Mexico, South, and Central America. The estimated number of CL per year still may range from 0.7–0 to 1.2 million. There is a decline in the number of estimated cases of the visceral form of the disease and may range from over 400,000 cases to less than 100,000 cases [6].
In the current review, we discuss about the various virulence factors of the different species of Leishmania and the strategies exploited by the parasites to overcome the immune defense mechanisms of the host for successful infection establishment. The review also highlights the current scenario of diagnosis, limitations of frontline drugs, and the therapeutic potential of immunomodulators in controlling the menace of leishmaniasis.
Life cycle, vector, and epidemiology
Leishmania is a group of protozoan parasites belonging to the Class Kinetoplastae and Order Trypanosomatida, which avails a digenetic life cycle involving an insect vector and a mammalian host [7].Leishmania sp can be characterized by the two prevailing forms, the elongated (10–20 μm) motile promastigote form and the oval-shaped (3–7 μm in diameter) non-motile amastigote form [7]. The promastigote form exists in the sand fly vector, where it undergoes various differentiation steps and transforms into the infective metacyclic promastigote form. These metacyclics are transmitted to mammalian hosts during the bite of the sand fly [8]. Amastigotes are the forms within the mammalian host, especially in phagocytic cells where they survive as intracellular parasites. When a sand fly vector bites an infected mammal, it ingests the amastigotes, which transform into the flagellated promastigote form on reaching the midgut of the insect. Eventually, the promastigotes move to the alimentary tract of the insect where they survive extracellularly and multiply by binary fission. The promastigotes then migrate towards the salivary glands and oesophagus and are later transmitted along with the insect saliva to the mammalian host during the next blood meal. The anticoagulant present in the saliva of the sand fly helps in the transmission by preventing the blood from coagulating at the site of insect bite. Post entry into the host, the promastigotes are readily taken up by macrophages or dendritic cells within which they revert back to the amastigote form and proliferate. This is followed by the eventual egress of the amastigotes from the host cells due to the host immune response-mediated cytolytic environment [9]. The amastigotes released are either phagocytosed by other macrophages or taken up by the sand fly during a blood meal. Thus, the parasite continues its life cycle and culminates in infection of surrounding cells and tissues in CL and organs rich in macrophages like the bone marrow, liver, and spleen in VL [10].
1-Kamran, M., Bhattacharjee, R., Das, S., Mukherjee, S., & Ali, N. (2023). The paradigm of intracellular parasite survival and drug resistance in leishmanial parasite through genome plasticity and epigenetics: Perception and future perspective. Frontiers in Cellular and Infection Microbiology, 13, 64.
2-Poulaki, A., Piperaki, E. T., & Voulgarelis, M. (2021). Effects of visceralising Leishmania on the spleen, liver, and bone marrow: A pathophysiological perspective. Microorganisms, 9(4), 759.
3-Gupta, A. K., Das, S., Kamran, M., Ejazi, S. A., & Ali, N. (2022). The pathogenicity and virulence of Leishmania-interplay of virulence factors with host defenses. Virulence, 13(1), 903-935.
4-Ghosh, S., & Dasgupta, R. (2022). Machine Learning and Neglected Tropical Diseases. In Machine Learning in Biological Sciences: Updates and Future Prospects (pp. 103-111). Singapore: Springer Nature Singapore.
5-Steverding, D. (2017). The history of leishmaniasis. Parasites & vectors, 10(1), 1-10.
6-Mitra, A. K., & Mawson, A. R. (2017). Neglected tropical diseases: epidemiology and global burden. Tropical medicine and infectious disease, 2(3), 36.
7-Gupta, A. K., Das, S., Kamran, M., Ejazi, S. A., & Ali, N. (2022). The pathogenicity and virulence of Leishmania-interplay of virulence factors with host defenses. Virulence, 13(1), 903-935.
8-Bates, P. A. (2007). Transmission of Leishmania metacyclic promastigotes by phlebotomine sand flies. International journal for parasitology, 37(10), 1097-1106.
9-Gupta, A. K., Das, S., Kamran, M., Ejazi, S. A., & Ali, N. (2022). The pathogenicity and virulence of Leishmania-interplay of virulence factors with host defenses. Virulence, 13(1), 903-935.
10-Gupta, A. K., Das, S., Kamran, M., Ejazi, S. A., & Ali, N. (2022). The pathogenicity and virulence of Leishmania-interplay of virulence factors with host defenses. Virulence, 13(1), 903-935.