Nonresponsiveness to standard treatment in cutaneous leishmaniasis: A case series from Sri Lanka

Refai, Fathima Wardha; Madarasingha, N. P.; Fernandopulle, Rohini; Karunaweera, Nadira D.

doi:10.4103/2229-5070.190835

Cited by 14 publications

(11 citation statements)

References 8 publications

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“…It is found to be genetically different from other established L. donovani strains in the world [ 3 – 5 ]. The clinicoepidemiological pattern of local diseases presents great variation, showing micro changes within the CL profile [ 6 ], atypical CL as a different clinical entity [ 7 ], and poorly responding cases [ 8 ]. Furthermore, expanding spatial dimensions [ 6 ] and presence of different and independent disease foci within the country [ 9 ] were identified recently, calling for urgent action.…”

Section: Introductionmentioning

confidence: 99%

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

Deepachandi

Weerasinghe

Ranasinghe

et al. 2020

BioMed Research International

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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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Section: Introductionmentioning

confidence: 99%

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

Deepachandi

Weerasinghe

Ranasinghe

et al. 2020

BioMed Research International

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“…A genetic variant of L. donovani, the usual cause of VL, has been reported to cause a large outbreak of CL in Sri Lanka since year 2001 [14–16]. Widening dimensions of CL outbreak [17–19], micro-changes within the continued profile of CL [20], varied risk factors for transmission [21], case clustering of CL in communities [22], poor treatment response [23], CL associated humoral response [24] and emergence of few MCL and VL cases [25–27], and species/strain variation [28] are of recent local concern. Urgent need for disease control has been highlighted at several occasions [29, 30].…”

Section: Introductionmentioning

confidence: 99%

Leishmania donovaniInduced Cutaneous Leishmaniasis: An Insight into Atypical Clinical Variants in Sri Lanka

Siriwardana

Deepachandi

Gunasekara

et al. 2019

Journal of Tropical Medicine

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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.

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“…Early disease confirmation and management is considered very important in disease control of L. donovani . Recent emergence of VL and MCL [9–11], poor treatment response [12], micro changes within CL profile [13], widening case distribution [8], atypical manifestations [12, 13], regionally varied risk factors [14–16] and questionnable potential for visceralization [17] further necessitates urgent action in this locality. Detection of all infections and all clinically apparent cases are important.…”

Section: Introductionmentioning

confidence: 99%

A highly sensitive modified nested PCR to enhance case detection in leishmaniasis

et al. 2019

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Background Human leishmaniasis is one of the major parasitic diseases with worldwide distribution. Sri Lanka is a recently established focus of leishmaniasis caused by a variant Leishmania donovani . Early case detection and management is a main approach identified for L. donovani control in the regional leishmaniasis elimination drive. Usefulness of light microscopy and in-vitro culture are limited in chronic, atypical or treated lesions though timely and accurate detection of all light microscopy/in-vitro culture negative cases of all forms of leishmaniasis is necessary for treatment. Timely treatment is important to minimize risk for death in visceral disease and undesired sequelae of long standing infection and illness on both patients and community. We described a 100% sensitive, Leishmania spp. specific modified version of a nested PCR (Mo-STNPCR) that also minimizes carry over and cross contaminations while facilitate investigation of light microscopy and in-vitro culture negative clinically suggestive cases of leishmaniasis. Methods Leishmania DNA was amplified using previously published P221: 5′-GGTTCCTTTCCTGATTTACG-3′ and P332: 5′-GGCCGGTAAAGGCCGAATAG-3’outer primers followed by a nested reaction using P223: 5′-TCCCATCGCAACCTCGGTT-3′ and P333: 5′-AAGCGGGCGCGGTGCTG-3′ inner primers that by passes the requirement of tube handling between the two steps of the conventional nested PCR. Leishmania DNA was detected in a range of infected tissue material. Infected material from patients with cutaneous leishmaniasis ( n = 30), visceral leishmaniasis ( n = 10) and from a control group including patients with non-leishmanial skin diseases ( n = 10), other systemic diseases ( n = 10) and healthy individuals ( n = 10) were examined with Mo-STNPCR. Results were further compared with those of light microscopy and in-vitro culture. Results Mo-STNPCR method was 100% sensitive and 100% specific for diagnosis of leishmaniasis. Light microscopy and in-vitro culture were positive in 75.0% ( n = 30/40) and 72.5% ( n = 29/40) samples respectively where combined results of them gave 87.5% ( n = 35/40) sensitivity. Mo-STNPCR did not cross react with control samples. Furthermore, Mo-STNPCR reduces the risk of cross-contaminations and carry over contaminations since the full reaction is carried out without opening the tubes. Per patient cost was calculated as 22 USD while the same was 3 and 6 USD for light microscopy and in-vitro culture respectively. Conclusion Mo-STNPCR method is a useful tool in detecting leishmaniasis in minority of cases that go undetected by first line investigations. ...

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Nonresponsiveness to standard treatment in cutaneous leishmaniasis: A case series from Sri Lanka

Cited by 14 publications

References 8 publications

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

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

Leishmania donovaniInduced Cutaneous Leishmaniasis: An Insight into Atypical Clinical Variants in Sri Lanka

A highly sensitive modified nested PCR to enhance case detection in leishmaniasis

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