To investigate the relationship of cutaneous leishmaniasis isolates from Sri Lanka to known species, we performed DNA sequencing and microsatellite analyses. We identified Leishmania donovani as the agent of Sri Lanka cutaneous leishmaniasis and showed that these parasites are closely related to those causing visceral leishmaniasis in the Indian subcontinent.

Sri Lanka is the newest reported focus of human leishmaniasis within the Indian subcontinent. Over the last 8 years, more than 2000 cases of cutaneous leishmaniasis (CL), apparently caused by Leishmania donovani (a species usually associated with the visceral form of the disease), have been passively identified in the country. The clinical profiles of 401 suspected cases of CL in Sri Lanka were recently explored and some of the cases' immunological responses were investigated, in antibody-detection assays based on the rk39 antigen. These studies were followed by cross-sectional surveys, involving active case detection, in three areas of Sri Lanka, two of them known to be at relatively high risk for CL, with the aims of estimating the local prevalences of the disease and identifying the main risk factors for its acquisition. This appears to be the first detailed report on the prevalence, risk factors and human serological response associated with human leishmaniasis in Sri Lanka. Although the data collected indicated that the transmission of the parasite causing CL was mostly outdoor (and possibly zoonotic) in the north of the country, most of the transmission in the south seemed to be peridomestic. The CL was found to affect a wide age range, in both male and female subjects. Curiously, the 24 cases of CL that were investigated in the rk39 assays gave negative results whereas the single cases of mucosal or visceral leishmaniasis that were studied were found positive for antibodies reacting with the rk39 antigen. More programmes of active case detection need to be launched across Sri Lanka before the true national burden posed by human leishmaniasis can be accurately evaluated. General awareness of leishmaniasis needs to be raised. Hopefully, continued research and disease monitoring will allow the effective control of leishmaniasis in Sri Lanka.

Visceral leishmaniasis is a vector-borne protozoan disease targeted for elimination from the Indian subcontinent by year 2020. Sri Lanka is a new focus of human leishmaniasis caused by a genetically distinct variant of Leishmania donovani, which is the species more widely known to cause visceral leishmaniasis (VL). The clinical entity that is most frequent in Sri Lanka is cutaneous leishmaniasis (CL), though a few cases of muco-cutaneous (MCL) and VL have also been reported in the recent past. In CL, papules, nodules, ulcerating nodules and ulcers occur mainly as single lesions on exposed body areas of affected individuals. A wide age range is affected including both sexes. The potential for visceralization in the cutaneous variant of L. donovani in Sri Lanka is not known. There is no evidence for a serological response in CL patients who have demonstrated negative for rK 39 antibodies in sera, (rk39 test being the recommended test for VL detection), while MCL and VL cases have been rK39 positive.Phlebotomus argentipes, the vector of L. donovani in other parts of the world is a widely prevalent insect in almost all parts of Sri Lanka. Studies are underway for vector identification. L.donovani is transmitted between this vector and the human host, the only known host for this species. However, domestic dogs have shown the presence of Leishmania parasites and also the presence of anti -L. donovani antibodies in their sera, providing primary evidence for the likely presence of an animal reservoir in Sri Lanka. Field-based risk factor studies have shown that there is peri-domestic as well as zoonotic/outdoor transmission cycles in different parts of the country.At present patients are detected mainly passively based on self referrals. Only a proportion of these patients proceed for pre-treatment laboratory confirmation due to the lack of freely available investigation facilities. Leishmaniasis was made a notifiable disease in Sri Lanka in 2008. Action plan for its control was drawn up with primary involvement of the Ministry of Health and other stake holders in 2008. Preventive and control activities are required to be put in place sooner rather than later. Enhanced case detection and active treatment are of prime value in controlling L.donovani infections. Availability of cost effective and field friendly diagnostic services in a decentralized manner, timely case management and vector control using appropriate protocols are necessary. To achieve this, a considerable amount of information is already available, and further research is needed to fill in the essential gaps.

Visceral leishmaniasis is recognized as an emerging health threat in Sri Lanka. At least a proportion of locally identified strains of L. donovani possess the ability to visceralize. Apparent anti leishmanial sensitivity is encouraging. Timely efforts in disease containment will be important in which accurate understanding of transmission characteristics, increased professional and community awareness, improved diagnostics and availability of appropriate treatment regimens.

Leishmaniasis is a neglected tropical disease transmitted by Phlebotomus spp. sand flies. Cutaneous leishmaniasis (CL) in Sri Lanka is caused by Leishmania donovani. Transmission patterns are different in Southern and Northern Sri Lanka. Current study examined the prevalence, risk factors and distribution of CL in Matara District, Southern Sri Lanka. Total of 2260 individuals from four District Secretariat divisions (DSDs) were screened by house to house surveys using an interviewer administered questionnaire. The study population had an age range of 1-90 years (median 5 43 + 17.31), low monthly income (v20 000 LKR, 52.8%) and a male to female ratio of 1 : 2. Thirty eight patients were diagnosed by light microscopy, culture and/or PCR with a disease prevalence of 1.68%. Spatial mapping provided evidence for significant case clustering, which tended to be more prominent with proximity to forest areas. The risk factors identified were un-plastered brick walls, absence or low usage of protective measures against insect bites, low income and excessive time (w4 hours/day) spent outdoors. However, exposure of limbs while outdoors, unawareness about the disease, type of occupation, common water source as the mode of water supply and presence of animal shelters within 200 m were not associated with the risk of acquiring the disease. Peri-domestic transmission is likely to contribute to the observed case clustering with all age groups at risk of acquiring the infection. Human behavioural habits coinciding with that of the vector, sand fly are likely to enable host-vector contact promoting its spread. Appropriate vector control measures, improvement of housing conditions, public education regarding preventive measures are required to contain the spread of disease.

SummaryThe visceralizing potential of apparently dermotropic Leishmania donovani in Sri Lanka (L. donovani-SL) was investigated through long-term follow-up of cutaneous leishmaniasis (CL) patients and in vivo and in vitro experimental infection models. CL patients (n = 250) treated effectively with intra-lesional antimony therapy were followed-up six monthly for 4 years. There was no clinical evidence of visceralization of infection (VL) during this period. Infection of BALB/c mice with L. donovani-SL (test) through intra-dermal route led to the development of cutaneous lesions at the site of inoculation with no signs of systemic dissemination, in contrast to the observations made in animals similarly infected with a visceralizing strain of L. donovani-1S (control). Cytokine (IL-10, IFN-γ) release patterns of splenocytes and lymph node cell cultures derived from mice primed with experimental infections (with either test or control parasites) revealed significantly high IFN-γ response associated with test mice with CL, while prominent IL-10 levels were observed in association with control mice with VL. Furthermore, diminished infection efficiency, intracellular growth and survival of L. donovani-SL parasites compared with L. donovani-1S were evident through in vitro macrophage infection experiments. These studies confirm, for the first time, the essential dermotropic nature of L. donovani-SL suggesting natural attenuation of virulence of local parasite strains.

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Cutaneous leishmaniasis (CL) was first detected in Sri Lanka in 1992.Local disease is caused by a genetically different variant of Leishmania donovani. Early case detection and management is the mainstay of L. donovani control. High degree of clinical suspicion is critical but a clinical diagnostic tool is not available for leishmaniasis. Current study described, for the first time, a two-staged clinical algorhythm that facilitates screening of CL in Sri Lanka by primary health care worker in stage 1 and management by medical professional in stage 2.Selected clinical markers of 400 patients suspected of CL were analysed retrospectively with laboratory confirmation of leishmaniasis. Ten clinical markers predicted CL with a over 90% accuracy. Subsets of markers showed high levels of sensitivities (60-97.2%) and/or significant association with positive laboratory results as compared to negative lesions [typical onset (acne-form, painless non-itchy), (P 5 0.026), size up to 2 cm (P 5 0.046), well-defined edges (P 5 0.002), regular edges (P 5 0.018), rounded shape (P 5 0.030), and lesions at 5-8 months (P 5 0.052)]. Five of them (typical onset, number up to 2, small size, rounded edges, and rounded shape) also had w 70% sensitivity levels as compared to laboratory findings. Typical onset had the highest sensitivity of 97% and a PPV of 72%. Lesions at 5-8 months duration having defined edges (P 5 0.013, specificity 89.7%, PPV 83.1) or having regular edges (P 5 0.006, specificity 86.2%, PPV 82.4%) were also predictive of CL. Most of early laboratory-confirmed (v12 months) lesions remained v3 cm (sensitivity w 67%, PPV w 70%) and had defined edges (sensitivity of 52-71%, specificity 46.7-68.8%), (PPV 75.1-86%). Four clinical markers served as good diagnostic markers in both early (j4) and late (w12 months) lesions, viz. typical onset (91.3-98.4%), presence of j2 lesions (sensitivity 82.6-94.7%), size j2 cm (66.9-73.7%), and regular edges (68.6-76.3%). Reliability of clinical markers generally declined in chronic lesions. However, small lesions of over 12 months were highly indicative of CL (sensitivity of 66%, specificity 66.7%). None of the single/combination markers, however, were 100% sensitive or specific, highlighting the undeniable usefulness of laboratory confirmation, in diagnosis. Decision-making algorithm used 10 basic clinical features for screening and seven specific clinical markers for clinical handling and referral for investigations.