scholarly journals First Evidence from Sri Lanka for Subphenotypic Diversity within L. donovani-Induced Classical Cutaneous Leishmaniasis

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Yamuna Siriwardana ◽  
Bhagya Deepachandi ◽  
Sudath Weerasinghe ◽  
Nadira Karunaweera ◽  
Chandanie Udagedara ◽  
...  
Keyword(s):  
Sri Lanka ◽  
Cutaneous Leishmaniasis ◽  
Host Response ◽  
Leishmania Donovani ◽  
Developmental Stages ◽  
Northern Region ◽  
Parasite Strain ◽  
Laboratory Confirmation ◽  
First Time ◽  
Transmission Foci

Sri Lanka reports a large focus of Leishmania donovani-induced cutaneous leishmaniasis (CL) with CL as the main clinical entity. Two independent, long existed, and clinicoepidemiologically different transmission foci in the northern region (NR) and southern region (SR) were recently reported. Current project is an extension to this previous study. Clinical diversity within a profile of classical cutaneous leishmaniasis (CCL) in a focus of L. donovani-induced CL is described for the first time. Patients with laboratory confirmed CCL ( n = 550 ) from NF and SF were evaluated. Lesions in both foci were found to have all classical developmental stages (small and large nodules, ulcerating nodules, and ulcers) and other identified changes (multiplication, ulceration, and enlargement). Main difference was in the proportions of lesions progressing in to each different stages, proportions of lesion undergoing the main changes, and in timing of these changes during the course of a lesion. Northern focus reported a smaller proportion of lesions showing enlargement and ulceration, and a longer period of time was also required for these changes when compared to same in southern focus. In northern focus, most lesions remained small and nonulcerating and showed a higher tendency to multiply while most lesions reported in southern focus enlarged and ulcerated rapidly and remained single. Current study also evidenced a wider spectrum in the rate and pattern of progression of a skin lesion and high individual variation which could mask these region-based differences. Parasitic, vector-related, or a host etiology is suggested. Slow progressing nonulcerating infections in North may be the result of a well-adopted parasite strain that coevolved with its host for a long period while inducing only a minimal host response. This could be one among many reasons for previously observed silent expansion in northern focus while southern focus remained more confined and stable over time. Small nonprogressive, nondisturbing lesions can play a major role as silent parasite reservoirs in a community. In addition, the laboratory detection rate declined significantly when lesions multiplied and enlarged indicating the need for early laboratory confirmation. Usefulness of identified features in clinical screening and management needs to be considered.

scholarly journals Leishmania donovani Induced Cutaneous Leishmaniasis: An Insight into Atypical Clinical Variants in Sri Lanka

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Yamuna Siriwardana ◽  
Bhagya Deepachandi ◽  
Chalukya Gunasekara ◽  
Wipula Warnasooriya ◽  
Nadira D. Karunaweera
Keyword(s):  
Sri Lanka ◽  
Head And Neck ◽  
Cutaneous Leishmaniasis ◽  
Disease Transmission ◽  
Leishmania Donovani ◽  
Developmental Stages ◽  
Clinical Entity ◽  
Delayed Treatment ◽  
Separate Clinical Entity ◽  
Study Laboratory

Sri Lanka is a recent focus having Leishmania donovani induced cutaneous leishmaniasis (CL) as the main clinical entity. A separate clinical entity within profile of CL was described in this study. Laboratory confirmed cases of CL (n= 950, 2002-2014) were analysed. Most lesions showed known classical developmental stages of CL (CCL) observed in other CL endemic settings while few cases (13%, 122/950) showed atypical skin manifestations (ACL). Clinical, geographical, and treatment response patterns of ACL were different from those of CCL. ACL was mainly found among males (68.0%), in 21-40 year age group (51.6%), and reported delayed treatment seeking (23.5% vs 16.3% in CCL), more nonclassical onset (lesions other than acne form <1cm sized papules), (12.1 vs 2.7%, P<0.05.), more head and neck lesions (41.5%. vs 27.2%), more large lesions (>4cm), (18.6 vs 9.9%), and poor laboratory positivity rates (65.6% vs 88.2%) when compared to CCL. When compared to lesions reporting a typical onset, lesions reporting nonclassical onset were more likely to develop ACL later on (50.1% vs 10.7%). As compared to lesions on limbs, those on head and neck and trunk were more likely to be ACL (7.0%, 16.3%, and 22.8%, respectively, P<0.05). ACL features were not age or gender dependent. Highest proportion within ACL category (32.8%) and small proportion of CCL (10.1%) originated from less leishmaniasis prevalent areas (other regions) (P<0.05). North reported more ACL than South (15.9% vs 7.4%). A total of 95 CL cases with a significant travel history were further analyzed. Residents of other regions when acquired infection from North or South developed more ACL than residents in North or South (60.9% vs 15.9% and 42.9% vs 7.4% respectively). Patients in other regions when travelled to North developed more ACL than when they travelled to South (60.9%, 42.9%). ACL and CCL required an average of 18 doses over 16.7 months and 10 doses over 12 weeks, respectively, to achieve a complete clinical cure. Underlying host immunological factors, parasite strain variations and regional variations of both could be underlying etiologies. Established independent transmission within less leishmaniasis prevalent regions combined with an unusual clinical picture leading to poor clinical suspicion and low laboratory confirmation rate will pose potential difficulties in early case detection in these highly populated and commercialized areas. This in turn will further facilitate silent and high disease transmission.

scholarly journals Trends in Recently Emerged Leishmania donovani Induced Cutaneous Leishmaniasis, Sri Lanka, for the First 13 Years

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Yamuna Siriwardana ◽  
Guofa Zhou ◽  
Bhagya Deepachandi ◽  
Janaka Akarawita ◽  
Chandanie Wickremarathne ◽  
...  
Keyword(s):  
Seasonal Variation ◽  
Sri Lanka ◽  
Cutaneous Leishmaniasis ◽  
Leishmania Donovani ◽  
Patient Characteristics ◽  
Poor Treatment ◽  
Scientific Platform ◽  
Epidemiological Trends ◽  
First Time

Sri Lanka reports a large epidemic of cutaneous leishmaniasis (CL) caused by an atypical L. donovani while regional leishmaniasis elimination drive aims at achieving its targets in 2020. Visceralization, mucotrophism, and CL associated poor treatment response were recently reported. Long-term clinico-epidemiological trends (2001-2013) in this focus were examined for the first time. Both constant and changing features were observed. Sociodemographic patient characteristics that differ significantly from those of country profile, microchanges within CL profile, spatial expansion, constant biannual seasonal variation, and nondependency of clinical profile on age or gender were evident. Classical CL remains the main clinical entity without clinical evidence for subsequent visceralization indicating presence of parasite strain variation. These observations make a scientific platform for disease control preferably timed based on seasonal variation and highlights the importance of periodic and continued surveillance of clinic-epidemiological and other characteristics.

scholarly journals Histopathology of Cutaneous Leishmaniasis Caused by Leishmania donovani in Sri Lanka

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Harshima Wijesinghe ◽  
Nayana Gunathilaka ◽  
Saveen Semege ◽  
Nishantha Pathirana ◽  
Nuwani Manamperi ◽  
...  
Keyword(s):  
Sri Lanka ◽  
Cutaneous Leishmaniasis ◽  
Leishmania Donovani ◽  
Clinical Presentation ◽  
Cross Sectional Study ◽  
Causative Organism ◽  
Variable Intensity ◽  
Cross Sectional ◽  
The North ◽  
Parasitic Load

Cutaneous leishmaniasis (CL) is a neglected tropical disease that is gaining importance in Sri Lanka and internationally. The clinical presentation, pathology, and method of parasite elimination in CL vary according to the species. Leishmania donovani is the causative organism for leishmaniasis in Sri Lanka. This collaborative cross-sectional study describes the clinicopathological features of cutaneous leishmaniasis among personnel of the tri-forces serving in the North and East of the country. The histology of fifty cases of CL confirmed by at least two methods (slit skin smear, lesion aspirate, tissue impression, and histology) was reviewed. The parasitic load was assessed semiquantitatively. The histological features were correlated with the clinical presentation and organism load. The majority (89.8%; n=44) presented with a single lesion mostly located in the upper limb (69.4%). The lesion types included papule (34.7%), nodule (32.7%), and an ulcer (30.6%). The evolution time of lesions averaged 31.55 weeks. Epidermal changes were observed in 49 of the biopsies and included hyperkeratosis (90.0%; n=45), acanthosis (44.0%; n=22), atrophy (34.0%; n=17), and interface change (66%; n=33). Dermal changes were seen in all cases and were characterized by a lymphohistioplasmacytic inflammatory infiltrate of variable intensity with ill-formed granuloma in 19 cases (38%) and well-formed epithelioid granulomas in 22 cases (44%). Focal necrosis was present in 20% (n=10). Leishmania amastigote forms were observed in 88% (n=44). Transepidermal elimination (P=0.025), granuloma (P=0.027) formation, and type of lesion (P=0.034) were significantly associated with the organism load. Granuloma formation was associated with a reduction in organism load, indicating that the macrophage activation played an important role in the control of the organism.

scholarly journals Evidence for Seroprevalence in Human Localized Cutaneous Leishmaniasis Caused byLeishmania donovaniin Sri Lanka

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Yamuna Deepani Siriwardana ◽  
Bhagya Deepachandi ◽  
Samantha Ranasinghe ◽  
Preethi Soysa ◽  
Nadira Karunaweera
Keyword(s):  
Sri Lanka ◽  
Cutaneous Leishmaniasis ◽  
Leishmania Donovani ◽  
Indian Subcontinent ◽  
Igg Antibodies ◽  
Major Health ◽  
Systemic Involvement ◽  
Number Of Patients ◽  
Nodular Lesions

Visceral leishmaniasis (VL) is considered as a major health threat in the Indian subcontinent.Leishmania donovani, a usually visceralizing species, causes cutaneous leishmaniasis (CL) in Sri Lanka. However, visceralizing potential of the localL. donovaniis not yet fully understood. This project studied the seroprevalence of local CL by using an in-house ELISA. An IgG-based ELISA using crudeLeishmaniaantigen (Ag) was developed and validated. A total of 50 laboratory confirmed cases of locally acquired CL were examined using the newly developed ELISA. According to the optimized ELISA, seroprevalence of anti-LeishmaniaIgG antibodies in the study group was 34.0% (n=17/50). Majority of seropositive individuals were males (n=13/17), representing 76%. Nearly half of the seropositive individuals were young adults (20–40 years,n=9/17, 53%). Higher proportions of single lesions, large lesions, and nodular lesions were associated with a seroconversion. A proportion of localL. donovaniinfections leading to CL have the ability to raise an antibody response in the host. This may indicate early systemic involvement as one possibility. Study of a large number of patients with adequate follow-up would be useful.

scholarly journals Genetic diversity of Leishmania donovani that causes cutaneous leishmaniasis in Sri Lanka: a cross sectional study with regional comparisons

2017 ◽  
Vol 17 (1) ◽  
Author(s):  
Udeshika Lakmini Kariyawasam ◽  
Angamuthu Selvapandiyan ◽  
Keshav Rai ◽  
Tasaduq Hussain Wani ◽  
Kavita Ahuja ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Sri Lanka ◽  
Cutaneous Leishmaniasis ◽  
Leishmania Donovani ◽  
Cross Sectional Study ◽  
Sectional Study ◽  
Cross Sectional ◽  
Regional Comparisons

scholarly journals Evidence that interspecies Leishmania hybrids contribute to changes in disease pathology

2020 ◽  
Author(s):  
Patrick Lypaczewski ◽  
Greg Matlashewski
Keyword(s):  
Sri Lanka ◽  
Visceral Leishmaniasis ◽  
Environmental Factors ◽  
Cutaneous Leishmaniasis ◽  
Leishmania Donovani ◽  
Genome Sequences ◽  
Geographic Locations ◽  
Diploid Genome ◽  
Cutaneous Disease ◽  
Visceral Disease

AbstractBackgroundLeishmaniasis is a widespread neglected tropical disease present in over 90 countries with diverse pathologies associated with different species of Leishmania parasites transmitted by infected sand flies. Leishmania donovani causes visceral leishmaniasis, a highly virulent fatal infection of the visceral organs. Leishmania major and Leishmania tropica cause less virulent cutaneous leishmaniasis where the infection remains in the skin at the site of the sandfly bite. A major molecular epidemiological question is why some variants of L. donovani in Sri Lanka cause cutaneous disease rather than the typical visceral disease.MethodsWhole genome sequencing data for 684 L. donovani samples was used to perform sequence alignments and worldwide phylogenetic analyses to determine the source of the atypical L. donovani strains from Sri Lanka. L. donovani genome sequences originating from Sri Lanka were further analyzed for evidence of hybridization with other Leishmania species by determining the density of heterozygous alleles. Polymorphisms from potential Leishmania hybrids were used to reconstruct the parental genetic sequences to identify the potential parental species and quantify their genetic contribution through sequence comparison of the reconstructed parental sequences with all Old World Leishmania genomes.FindingsHere we show that L. donovani in Sri Lanka contains genes with widespread gene polymorphisms derived from African L. major and L. tropica genomes that were likely obtained as a result of diploid genome hybridization and recombination resulting in progeny with mosaic genomes. Furthermore, evidence is presented that multiple L. donovani hybrid parasites originating from visceral leishmaniasis endemic Africa have entered Sri Lanka yet visceral leishmaniasis remains non-existent raising the possibility that environmental factors favour the establishment of atypical L. donovani strains in Sri Lanka.InterpretationThe discovery of L. major and L. tropica genome sequences in L. donovani provides a compelling rationale how some L. donovani strains in Sri Lanka may be able to cause cutaneous rather than visceral leishmaniasis. The identification of L. donovani hybrid parasites in cutaneous leishmaniasis lesions provides a unique opportunity to investigate environmental and parasite genetic factors controlling disease epidemiology and pathogenesis.FundingCanadian Institutes of Health Research and Fonds de recherche du Québec – SantéResearch in contextEvidence before this studyDifferent Leishmania species parasites cause either benign cutaneous leishmaniasis or fatal visceral leishmaniasis. It is unknown why some variants of Leishmania donovani that typically causes visceral leishmaniasis in Asia and Africa can cause cutaneous leishmaniasis in specific geographic locations including Sri Lanka. Leishmania has a diploid genome and hybrid parasites have been identified in nature and generated experimentally. In the context of this study, hybrids are considered to be progeny derived from a single outcross event between two diverse parents. Uncertainty remains whether interspecies hybrids with visceral and cutaneous leishmaniasis causing species in nature are associated with different disease outcomes.Added value of this studyEvidence for genetic hybridization between visceral and cutaneous disease causing Leishmania species is described from Sri Lanka where cutaneous leishmaniasis is highly endemic yet there is no ongoing visceral leishmaniasis transmission. This provides a potential explanation how L. donovani can become attenuated for visceral disease and could help to identify geographic environmental factors associated with selection for parasite attenuation.Implications of all the available evidenceHybrid Leishmania parasites may be one source of atypical cutaneous leishmaniasis. Epidemiological studies are needed to determine why diverse L. donovani hybrid parasites have become ubiquitous in specific geographic locations where the incidence of cutaneous leishmaniasis is increasing. This has implications for understanding the genetic control of disease pathogenesis and for the prevention of cutaneous or visceral leishmaniasis locally and in neighboring countries.

scholarly journals Assessment of intralesional cytokine profile of cutaneous leishmaniasis caused by Leishmania donovani in Sri Lanka

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Lahiru Sandaruwan Galgamuwa ◽  
Buthsiri Sumanasena ◽  
Devika Iddawela ◽  
Susiji Wickramasinghe ◽  
Lalani Yatawara
Keyword(s):  
Sri Lanka ◽  
Cutaneous Leishmaniasis ◽  
Leishmania Donovani ◽  
Cytokine Profile

scholarly journals First Serological Study Revealing High Humoral Response and Evidence for Antigenic Heterogeneity in Leishmania donovani Induced CL in Sri Lanka

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Bhagya Deepachandi ◽  
Sudath Weerasinghe ◽  
Samantha Ranasinghe ◽  
Thisira P. Andrahennadi ◽  
Mahendra N. Wickramanayake ◽  
...  
Keyword(s):  
Sri Lanka ◽  
Cutaneous Leishmaniasis ◽  
Leishmania Donovani ◽  
Skin Diseases ◽  
Cost Comparison ◽  
Enzyme Linked Immunosorbent Assay ◽  
Serological Response ◽  
Healthy Controls ◽  
Case Detection ◽  
Predictive Values

Posing a threat to the ongoing leishmaniasis elimination efforts in the Indian subcontinent, L. donovani-induced cutaneous leishmaniasis (CL) has been recently reported in many countries. Sri Lanka reports a large focus of human cutaneous leishmaniasis (CL) caused by Leishmania donovani, a usually visceralizing parasite. Enhanced case detection, early treatment, and in-depth understanding of sequalae are required to contain the spread of disease. Visceralizing potential of dermotropic strains has not been fully ruled out. Sri Lankan strains have shown a poor response to established serological assays. The present concern was to develop an in-house serological assay and to determine the seroprevalence of CL for identifying visceralizing potential and its usefulness in enhancing case detection. Crude cell lysate of dermotropic L. donovani promastigotes-based indirect enzyme-linked immunosorbent assay (ELISA) was previously optimized. Assay was evaluated using sera from 200 CL patients, 50 endemic and 50 nonendemic healthy controls, 50 patients with other skin diseases, and 50 patients with other systemic diseases. Seroprevalence and clinicoepidemiological associations were analyzed. Assay was compared with light microscopy (LM) and in vitro culturing (IVC). Cost comparison was carried out. Seroprevalence of CL was 82.0%. The assay had 99.5% specificity, and all healthy controls were negative at 0.189 cut-off. Positive and negative predictive values were 99.4% and 84.7%, respectively. Positivity obtained in ELISA was comparable to LM and higher than that of IVC. Cost per patient was 3.0 USD for both ELISA and LM and 6.0 USD for IVC. Infections occurring in all age groups and both genders demonstrated >75.0% of seropositivity. Patients had lesions with different durations/types/sizes showed >70.0% of seropositivity. Study identified a high seroprevalence of L. donovani-induced CL for the first time, indicating potential for visceralization or transient serological response. This can be used as a second line test in LM-negative CL cases to enhance clinical case detection. Further studies are warranted to examine in-depth correlations, antigen profiles, comparison with other established serological tools, and usefulness in the detection of asymptomatic cases. (National patent LK/P/1/19697).

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