Trends in Recently Emerged<i> Leishmania donovani</i> Induced Cutaneous Leishmaniasis, Sri Lanka, for the First 13 Years

Siriwardana, Yamuna Deepani; Zhou, Guofa; Deepachandi, Bhagya; Akarawita, J.; Wickremarathne, Chandanie; Warnasuriya, Wipula; Udagedara, Chandanie; Ranawaka, Ranthilaka R.; Kahawita, Indira; Ariyawansa, Dananja; Sirimanna, Ganga; Chandrawansa, P. H.; Karunaweera, Nadira D.

doi:10.1155/2019/4093603

Cited by 29 publications

(31 citation statements)

References 30 publications

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“…The evidence presented herein for the existence of 4 different populations of L. donovani parasites in Sri Lanka (SL1, SL2A, SL2B and SL3) could help reconciliate differences in lesion morphology 40,41 , spatial distribution 20 and drug susceptibility 26 previously reported across Sri Lanka. Indeed, parasites causing lesions that share features of L major or L. tropica infection 40 or with variable tolerance to sodium stibogluconate 26 could consist of different L. donovani hybrids with varying amount of genes from either L. major or L. tropica as they have different pathological features 42 and drug sensitivity 43 .…”

Section: Discussionsupporting

confidence: 61%

Evidence that interspeciesLeishmaniahybrids contribute to changes in disease pathology

Lypaczewski

Matlashewski

2020

Preprint

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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.

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Section: Discussionsupporting

confidence: 61%

Evidence that interspeciesLeishmaniahybrids contribute to changes in disease pathology

Lypaczewski

Matlashewski

2020

Preprint

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“…Similar to past reports, CL was found to affect a broad age range (2-77 years) and both genders with a slight adult male preponderance [35]. However, the recent disease trends of increased female and older adult involvement documented by Siriwardane et al, was noted [35]. Most of those affected were housewives, unskilled workers and school children who engaged in outdoor activities such as home gardening (housewives, unskilled workers and pensioners) and sports activities (school children).…”

Section: Entomological Data On Vector Prevalencesupporting

confidence: 90%

Section: Entomological Data On Vector Prevalencesupporting

confidence: 84%

Epidemiology of cutaneous leishmaniasis in a newly emerging focus in Gampaha district, Western province of Sri Lanka

Mallawarachchi¹,

Chandrasena²,

Wijerathna³

et al. 2020

Preprint

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Background: Cutaneous leishmaniasis (CL) appears to be spreading to previously non-endemic regions of Sri Lanka. The aim of this study was to describe a newly emerging focus of CL in the district of Gampaha, in Western Sri Lanka. Methods: A case based descriptive study was carried out from January 2018 to April 2019 in the Mirigama Medical Officer of Health (MOH) area, which reported the highest number of CL cases in Gampaha District. Laboratory confirmed cases were traced and socio-demographic and clinical data were collected via a validated questionnaire and clinic records respectively. The quality of life (QOL) of study participants was measured using the Dermatology Life Quality Index (DLQI). Global Positioning System (GPS) coordinates of patient residences were recorded using handheld GPS receivers. Sand-flies were collected from four selected sites, using Indoor Hand Collection (IHC) (162 units) and Cattle Baited Net Traps (CBNT) (n = 3) and a battery-operated aspirator. Results: Of 73 patients identified in this study, 58.9% were males, with a mean age of 43.6 years (SD 20.1). The lesions included nodules (52.05%) and ulcers (47.9%). Single lesions were seen in 69.86%, while 30.1% had multiple. Except for one mucosal lesion, all others were on skin. Treatment varied from sodium stibogluconate (SSG) + cryotherapy (46.57%), SSG (45.2%) and cryotherapy (8.2%). Patients with multiple lesions were more likely to be treated with combined SSG + cryotherapy (p < 0.05). The mean DLQI score was 8.14 (SD = 7). Most patients engaged in outdoor activities that exposed them to the risk of sand-fly bites Workplaces of 81.1% (27/33) were located within the district. Housing conditions of study participants were of moderate (59%), good (35.6%) and poor (5%) quality. Four households reported multiple cases. Spatial distribution of cases indicated notable clustering in seven adjacently located Public Health Inspector (PHI) areas. Phlebotomus argentipes was detected in all CBNTs and 35.28% of IHC units surveyed. Conclusions: CL is emerging in Gamapha district with Mirigama MOH area being the epicentre of infection. The disease had a moderately negative impact on QOL of patients. Minimal migration of cases, clustering of cases within households and in the locality indicates local transmission with P. argentipes as the probable vector.

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“…7 The main clinical form remains as CL in this focus. 8,9 Sri Lanka has two main foci for transmission of leishmaniasis in the north and south. 9 In 2008, leishmaniasis was made a notifiable disease in Sri Lanka.…”

Section: Introductionmentioning

confidence: 99%

“…8,9 Sri Lanka has two main foci for transmission of leishmaniasis in the north and south. 9 In 2008, leishmaniasis was made a notifiable disease in Sri Lanka. 10 Establishment of more dangerous forms (VL, MCL) 11 , the presence of locally acquired mucosal leishmaniasis 12 and a humoral response associated with CL 13 have been reported recently.…”

Section: Introductionmentioning

confidence: 99%

Literature review and a preliminary study on leishmaniasis to inform community awareness campaigns in Sri Lanka

Chandrasiri

Chandrasinghe

Chathuranga

et al. 2019

Sri Lankan J Infec Dis

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

Cited by 29 publications

References 30 publications

Evidence that interspeciesLeishmaniahybrids contribute to changes in disease pathology

Evidence that interspeciesLeishmaniahybrids contribute to changes in disease pathology

Epidemiology of cutaneous leishmaniasis in a newly emerging focus in Gampaha district, Western province of Sri Lanka

Literature review and a preliminary study on leishmaniasis to inform community awareness campaigns in Sri Lanka

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