The global disease burden due to leishmaniasis is high with as many as 12 million people currently infected, and 1-2 million new cases occurring each year, particularly in Africa, Asia and South America. It is considered as one of the least studied and most neglected of tropical diseases. The causative agent belongs to the genus Leishmania and it is transmitted via the bite of an infected phlebotomine sand fly. Over 20 species of Leishmania are known to cause diseases, which ranges from self-limiting cutaneous lesions to potentially fatal visceral disease, mainly depending on the causative parasite species. The most virulent form of disease is caused by L.donovani that is mostly prevalent in the Indian subcontinent and its pathogenetic mechanisms, particularly with regard to its phenotypic variants remain poorly understood. Sri Lanka is a new focus affected by leishmaniasis with the evidence gathered so far pointing towards the presence of genetically distinct strains of L.donovani that demonstrates an atypical phenotypic property of dermotropism, which is proposed here to be studied in depth using clinical, biological and latest molecular techniques. In depth understanding of such strain variations within the L.donovani species would enable better understanding of the virulent properties of this species and in turn would lead to the development of more efficient diagnostics and effective treatment methods in the future. The broad objective of this proposal is to study the phenotypic and genotypic characteristics of L.donovani that cause cutaneous leishmaniasis (CL) in Sri Lanka. Specifically, the essential dermotropic nature of the parasites will be determined through studies on the clinical/pathological sequelae of CL by long-term follow up of patients using clinical and serological criteria. Secondly, to study in vivo and in vitro correlates of parasite virulence, viz macrophage invasion and disease sequalae in established animal models. Thirdly, detailed genetic characterizations of local L.donovani strains is proposed to be done using Leishmania mini-circle DNA footprint assay, which has been established by the US collaborators, as an efficient and effective method to differentiate inter and intra-species sequence variations. Hence, this assay would enable in depth genetic characterization of parasite isolates that cause CL in Sri Lanka when analyzed together with similar data from strains that cause visceral disease in India and Nepal. Overall, this study is meant to enable better understanding of the pathogenicity of L.donovani, which in the long term would help reduce the global disease burden contributing positively towards the disease elimination efforts in the Indian subcontinent.

Public Health Relevance

Leishmaniasis is one of the least studied and most neglected of tropical diseases in spite of the high morbidity and mortality it causes, especially in poor communities in the developing world. Better understanding of the genetic structure and its changes in the causative parasite, the objective of this proposed study, would enable the development of efficient and effective tools to assist control strategies to combat this devastating disease and enhance the elimination efforts that are in place in the Indian subcontinent with overall effect of reducing the global disease burden.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI099602-05
Application #
9124713
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Rao, Malla R
Project Start
2012-08-15
Project End
2017-07-31
Budget Start
2016-08-01
Budget End
2017-07-31
Support Year
5
Fiscal Year
2016
Total Cost
Indirect Cost
Name
University of Colombo
Department
Type
DUNS #
659410638
City
Colombo
State
Country
Sri Lanka
Zip Code
300
Refai, Wardha F; Madarasingha, Nayani P; Sumanasena, Buthsiri et al. (2018) Cutaneous leishmaniasis in Sri Lanka: effect on quality of life. Int J Dermatol 57:1442-1446
Karunaweera, Nadira D; Ferreira, Marcelo U (2018) Leishmaniasis: current challenges and prospects for elimination with special focus on the South Asian region. Parasitology 145:425-429
Kariyawasam, K K G D U L; Selvapandiyan, A; Siriwardana, H V Y D et al. (2018) Dermotropic Leishmania donovani in Sri Lanka: visceralizing potential in clinical and preclinical studies. Parasitology 145:443-452
Manamperi, Nuwani H; Chandu de Silva, M V; Pathirana, Nishantha et al. (2018) Tissue Impression Smears as a Supplementary Diagnostic Method for Histopathology in Cutaneous Leishmaniasis in Sri Lanka. Am J Trop Med Hyg 98:759-762
Siriwardana, Yamuna Deepani; Deepachandi, Bhagya; Ranasinghe, Samantha et al. (2018) Evidence for Seroprevalence in Human Localized Cutaneous Leishmaniasis Caused by Leishmania donovani in Sri Lanka. Biomed Res Int 2018:9320367
Refai, Wardha F; Madarasingha, Nayani P; Sumanasena, Buthsiri et al. (2017) Efficacy, Safety and Cost-Effectiveness of Thermotherapy in the Treatment of Leishmania donovani-Induced Cutaneous Leishmaniasis: A Randomized Controlled Clinical Trial. Am J Trop Med Hyg 97:1120-1126
Manamperi, N H; Oghumu, S; Pathirana, N et al. (2017) In situ immunopathological changes in cutaneous leishmaniasis due to Leishmania donovani. Parasite Immunol 39:
Siriwardana, H V Y D; Karunanayake, P; Goonerathne, L et al. (2017) Emergence of visceral leishmaniasis in Sri Lanka: a newly established health threat. Pathog Glob Health 111:317-326
Kariyawasam, Udeshika Lakmini; Selvapandiyan, Angamuthu; Rai, Keshav et al. (2017) Genetic diversity of Leishmania donovani that causes cutaneous leishmaniasis in Sri Lanka: a cross sectional study with regional comparisons. BMC Infect Dis 17:791
Karunaweera, Nadira D (2016) Leishmaniasis: Path toward elimination from the Indian subcontinent. Trop Parasitol 6:2-4

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