Visceral Leishmaniasis Elimination Research Articles

Nationwide cross-sectional surveillance of Leishmania donovani in phlebotomine sand flies and its impact on national kala-azar elimination in India

Nationwide cross-sectional surveillance of Leishmania donovani in phlebotomine sand flies and its impact on national kala-azar elimination in India

Atypical cutaneous leishmaniasis: a new challenge to VL elimination in South-East Asia

Visceral leishmaniasis (VL) caused by L. donovani in South-East Asian endemic countries including India, Nepal and Bangladesh has been the primary focus of the ongoing VL elimination program. With a major reduction in VL cases resulting from the elimination program during the last two decades, the efforts are now focused on the challenges posed by potential reservoirs within the asymptomatic cases, HIV-co-infection VL cases and Post Kala-azar Dermal Leishmaniasis (PKDL) cases that continue to sustain the parasite transmission cycle in known and newer endemic zones. This article brings attention to a new potential parasite reservoir in the form of atypical cutaneous leishmaniasis (ACL) cases caused by novel L. donovani genetic variants. L. donovani mediated ACL is an emerging phenomenon in recent endemic sites that now justify a need for implementing molecular surveillance tools to identify region-specific L. donovani variants with dermotropic capabilities and potential to revert to visceral disease. A timely detection of novel ACL causing L. donovani genetic lineages in South-East Asian endemic regions is necessary to halt the spread of ACL and is potentially crucial for the sustainability of the advances made by the VL elimination.

Visceral Leishmaniasis in Sub-Himalayan India (1967-2023): A Systematic Review.

Substantial gains have been achieved in the control of visceral leishmaniasis (VL) in the four endemic states of India; however, cases are sporadically reported from other nonendemic regions of India such as the sub-Himalayan region, which can be a hurdle to VL elimination. We analyzed VL reports published from the sub-Himalayan regions of India over seven decades (1967-2023) in this systematic review. Medline, Embase, Scopus, and Web of Science were searched for VL cases from sub-Himalayan regions of India. The demographic data, clinical presentation, diagnostic modality, treatment, outcomes of the cases, and overall year-wise and geographical distribution of the cases were analyzed; studies on the sand fly vector were also included. From 535 articles, 33 studies were included in the analysis. Overall, 228 patients were diagnosed with VL in the sub-Himalayan region of India from 1967 to 2023. These cases were reported from Uttarakhand (n = 178), Himachal Pradesh (n = 39), and Jammu and Kashmir (n = 11). Most patients (88.4%) did not have a history of travel outside their native places. Three pediatric cases were reported from Jammu and Kashmir. The DNA of Leishmania donovani was detected in four of the 52 (7.7%) sand flies collected from Himachal Pradesh. The published literature points toward the existence of local transmission of VL in the sub-Himalayan region of India, strongly substantiated by the emergence of pediatric VL in some places. Thus, these difficult-to-reach hilly states of India will require focused surveillance for VL to successfully achieve elimination goals.

Post kala-azar dermal leishmaniasis burden at the village level in selected high visceral leishmaniasis endemic upazilas in Bangladesh

ObjectivesAs post kala-azar Dermal Leishmaniasis (PKDL) threatens the success of the Visceral Leishmaniasis (VL) elimination initiative, we aimed to investigate the PKDL burden, including an active search for PKDL in leprosy-negative skin lesion cases. We also investigated their health-seeking behavior and perceived level of stigma. MethodsThis was a cross-sectional survey among inhabitants in the VL-endemic villages of the five most VL-endemic upazilas. VL experts trained medical officers in Upazila Health Complexes (UHCs) and leprosy facilities in PKDL management. Frontline workers conducted house-to-house surveys, referring PKDL suspects to designated centers. Data analysis involved Epi Info version 7 and IBM SPSS Statistics 25. ResultsAmong 472,435 screened individuals, 4022 had past VL (0.85 %). Among the screened population, 82 were PKDL suspects, and 62 PKDL cases were confirmed. The overall PKDL burden was 1.3 (95 % CI: 1.0-1.7) in the 10,000 population in the endemic villages. Male predominance and macular form of PKDL were observed. Thirty-nine PKDL patients perceived stigma of different levels. Only 27 of 62 (44 %) had received PKDL treatment. Medicine's unavailability and side effects were a major reason behind treatment interruption. Active screening among 137 leprosy-negative PKDL suspects yielded 10 (7.3 %) PKDL cases. ConclusionThe existence of PKDL cases in the VL endemic areas is a concern as those are inter-epidemic reservoirs. As per the WHO roadmap, the PKDL burden must be reduced by 70 % and 100 %, respectively, by 2026 and 2030. NKEP can take the current burden of 1.3 per 10,000 people in VL endemic villages as a baseline. Integrating active case detection for PKDL in leprosy hospitals and screening centers is feasible and worth deploying nationwide.

Challenges in the Treatment of Coinfection of Visceral Leishmaniosis and Hepatitis B/C Viruses

There is a significant research gap in India due to incomplete investigation of seroprevalence of co-infection with visceral leishmaniasis (VL), hepatitis B (HBV) and hepatitis C (HCV). This study attempts to fill this gap by providing an in-depth analysis of the prevalence and consequences of these co-infections. The study of 32 VL patients revealed that 28 (8.88%) tested positive for HBV, 1 (0.317%) for HCV and 3 (0.95%) for both HBV and HCV. These results highlight how difficult it is to treat people with two diseases at the same time. An example of how co-infection makes treatment much more difficult is the fact that a patient with both VL and HBV required six courses of anti-leishmaniasis medication. The study shows how important it is for VL patients to be tested regularly for HBV and HCV to improve treatment response and support India's plan to get rid of kala-azar. Accurate identification of co-infections is necessary to reduce the overall burden of the disease and develop effective treatment regimens. Systematic testing of VL patients for HBV and HCV not only helps in controlling and perhaps even eliminating kala-azar, but also makes it easier to treat each patient as an individual, improving their health. In areas where viral hepatitis is prevalent, this strategy is particularly important as these diseases represent a double burden on public health. Implementing integrated treatment regimens and routine screening can reduce the impact of co-infection and advance the public health goal of kala-azar elimination. To improve patient outcomes and advance public health goals, the results of this study strongly support the integration of comprehensive screening programs into existing healthcare systems to improve the treatment of VL patients.

The nexus between Leishmania & HIV: Debilitating host immunity and Hastening Comorbid disease burden

The scintillating association between Leishmania and HIV has contributed exceptionally towards expansion of Visceral Leishmaniasis (VL) with Acquired Immunodeficiency Syndrome (AIDS). The co-infection poses a grievous threat to elimination of VL and containment of Human Immunodeficiency Virus (HIV). When coinfected, Leishmania and HIV complement each other's proliferation and survival by inducing immunesenescence, T cell fatigue and exhaustion. Antigen presentation is lost, co-stimulatory molecules are diminished whereas co-inhibitory molecules such as CTLA-4, TIGIT, LAG-3 etc. are upregulated to ensure a Th2-baised immune environment. As a consequence, Leishmania-HIV coinfection causes poor outcomes, inflates the spread of Leishmania parasites, enhances the severity of side-effects to drugs, as well as escalate the probability of treatment failure and mortality. What makes control extremely strenuous is that there are frequent episodes of VL relapse with no prognostic markers, no standard immunophenotype(s) and appearance of atypical clinical symptoms. Thus, a standard therapeutic regimen has been difficult to develop and treatment is majorly dependent upon a combination of liposomal Amphotericin B and Miltefosine, a therapy that is expensive and capable of causing drastic side-effects in recipients. As World Health Organization is committed to eliminate both VL and HIV in due course of future, the existing therapeutic interventions require advancements to grapple and overcome this hazardous co-infection. In this context, an overview of HIV-VL co-infection, immunopathology of HIV and Leishmania co-inhabitance, available therapeutic options and their limitations in the treatment of co-infection are discussed in-depth.

Leishmaniases in Ethiopia: a scoping review protocol to determine the scope of research and remaining gaps

IntroductionThe leishmaniases are among the group of neglected tropical diseases that cause significant morbidity and mortality each year. Currently, the East Africa region has the highest visceral leishmaniasis burden in...

Rising case-fatality rate of kala-azar (visceral leishmaniasis) in India: An unexpected challenge to the kala-azar elimination program?

The target of kala-azar elimination was initially set in 2010 and was later extended several times to finally be fixed in 2020, which also passed without success. However, in 2022, India had come very close to complete elimination by achieving a 98.7% decline in kala-azar cases. While, at the final moments of achieving the long-awaited target of elimination of kala-azar from India, the unexpected rise in the case-fatality rate from 2017 needs to be addressed.

Prevalence of hepatitis B and C virus infections among visceral leishmaniasis patients: a systematic review and meta-analysis.

Visceral leishmaniasis (VL) patients are at high risk of acquiring hepatitis B virus (HBV) and hepatitis C virus (HCV) infections during multiple injections and the anti-leishmanial treatment possesses a potential hepatotoxic effect. This systematic review and meta-analysis determined the pooled prevalence of HBV and HCV infections in VL patients. This study was registered in the International Prospective Register of Systematic Reviews (PROSPERO), with the assigned number CRD42024516889, and conducted as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A literature search was performed using PubMed, Medline, EMBASE, Google Scholar, Web of Science, and Science Direct databases. Data were extracted using Microsoft Excel and analyzed using STATA version 11.0 software. A random-effects model was used to estimate the pooled effect size of outcome variables across studies with a 95% confidence interval and was displayed in a forest plot. The I 2 statistic was used to check for heterogeneity. The presence of publication bias was determined using a funnel plot and Egger's test with a p value <0.05 evidence of statistically significant bias. Among 216 retrieved records, seven studies were eligible for systematic review and meta-analysis. A total of 937 VL patients were examined, revealing that 105 and 93 were infected with HBV and HCV, respectively. The pooled prevalence of HBV was 16.15% (95% CI: -4.10 to 36.39), with a significant heterogeneity (I 2 = 91.4%, p < 0.001). The combined prevalence of HCV was 13.74% (95% CI: 1.32-26.16, I 2 = 71.6%, p = 0.003). The funnel plot (symmetry), and Egger's test in both HBV (p value = 0.650) and HCV (p value = 0.841) revealed no publication bias. In subgroup analysis, high HBV and HCV prevalence was detected in Sudan; 20.64% (95% CI: -13.60 to 54.88) and India; 18.26% (95% CI: -0.40 to 36.92%), respectively. This study revealed a high prevalence of both HBV and HCV infections in VL patients. In subgroup analysis, the prevalence of HBV and HCV was high in Sudan and India, respectively. Therefore, screening of VL patients for HBV and HCV, vaccination of VL patients in endemic regions, and collaboration between kala-azar and hepatitis elimination programs are required. https://www.crd.york.ac.uk/prospero/export_details_pdf.php#page=1.00&gsr=0, identifier: CRD42024516889.

Monitoring of Leishmania transmission in the postelimination phase: The potential of serological surveys

ObjectivesMonitoring of Leishmania transmission is considered a strategic priority for sustaining elimination of visceral leishmaniasis as a public health problem in the Indian subcontinent. The objective of this study was to evaluate whether serological surveys can distinguish between communities with and without Leishmania transmission, and to assess which serological marker performs best. MethodsSeven villages were selected from Bihar and Uttar Pradesh state, India, and categorized as either currently endemic (CE), previously endemic (PE) or nonendemic (NE). Blood samples were analyzed with the rK39 RDT, direct agglutination test (DAT), and rK39 ELISA. ResultsContrary to the rK39 RDT and DAT, the rK39 ELISA showed a significant difference between all three categories of endemicity, with a seroprevalence of 5.21% in CE villages, 1.55% in PE villages, and 0.13% in NE villages. Even when only looking at the seroprevalence among children aged <10 years, the rK39 ELISA was still able to differentiate between villages with and without ongoing transmission. ConclusionOur findings suggest the rK39 ELISA to be the most promising marker for monitoring of Leishmania transmission. Further validation is required, and practical, context-adapted recommendations need to be formulated in order to guide policymakers toward meaningful and sustainable surveillance strategies in the post-elimination phase.

Active Community-Based Case Finding of Endemic Leishmaniasis in West Bengal, India

IntroductionThe ongoing visceral leishmaniasis (VL) elimination programme in India is targeting the elimination of the disease VL but not the pathogen. The persistence of hidden parasite pool may initiate a resurgence in suitable conditions. This study dealt with a novel approach to unearth such pathogen pool and their proper management to prevent the resurgence of VL.Materials and MethodsWe deployed a new approach for detection of pathogen pool by following up the VL and post kala-azar dermal leishmaniasis patients treated during the last 10 years along with mass sero-surveillance within a radius of 500 m of recently treated individuals.ResultsWe followed up 72.6% (3026/4168) previously treated VL and post kala-azar dermal leishmaniasis patients and diagnosed 42 (1.4%) new and 38 (1.3%) recurrent post kala-azar dermal leishmaniasis. We detected 93 asymptomatic leishmanial infection, 8 VL and 1 post kala-azar dermal leishmaniasis by mass sero-surveillance.ConclusionOur three-step process including mapping and follow-up of previously treated cases, mass surveillance within 500 m of radius of known cases, and 6 monthly follow-on clinical and serological screening of asymptomatic cases, enabled detection of previously undetected cases of post kala-azar dermal leishmaniasis and VL. Recurrent post kala-azar dermal leishmaniasis deserves special attention regarding their treatment guideline. Early diagnosis and effective treatment of all leishmaniasis cases will hasten pathogen elimination and prevent resurgence of VL. This may help the policymakers to develop appropriate strategy for elimination of pathogen to prevent resurgence of VL.

Distribution and Seasonal Variation of Phlebotomus and Sergentomyia Sand Fly Populations in Bhutan.

Leishmaniasis is considered one of the neglected tropical diseases in the world. Although Bhutan is a member of the visceral leishmaniasis elimination consortium in South Asia, not much attention has been accorded to the disease because of its low incidence. The vector that transmits Leishmania remains poorly understood. In this backdrop, sand-fly surveys were regularly conducted at multiple sites where leishmaniasis cases have been reported in Bhutan. Collections were made using CDC light traps and cattle-baited net traps in 15 villages from February 2019 to May 2022. Six species of Phlebotomus and four species of Sergentomyia were identified from these sites that included two Phlebotomus and three Sergentomyia species discovered for the first time in Bhutan. Sand-fly density varied significantly from village to village, and it showed strong seasonality with peak numbers collected from June to October and almost zero from December to February. Overall, sand-fly density was highest in the basements of the houses and were higher outdoors than indoors. Cattle-baited net traps collected few sand flies during the surveillance period. This work constituted the first systematic sand-fly population surveillance conducted in Bhutan and will provide a baseline for future vector ecology and Leishmania epidemiological studies.

The one health approach: combating the persistent Visceral Leishmaniasis (Kala-azar) outbreaks in Isiolo County, Kenya

Background: Visceral leishmaniasis has remained a public health problem in Kenya despite Ministry of Health’s numerous efforts. This is associated with absence of a multidisciplinary response to outbreaks. We intended to analyze community’s prioritization of causes of Visceral leishmaniasis as well as community awareness on the disease prevention and control. Methods: This was a descriptive cross-sectional study design conducted between September 2023 to December 2023. 433 households’ heads, 23 community leaders and health workers were study informants. Results: Study findings showed clear proximity of human settlements and socioeconomic activities to the vector sandfly breeding sites. Environmental factors augmented by effects of climate change including flooding and high temperatures have sustained transmission including emergence of the disease in new foci. Low socio-economic status, environmental factors and climate change effects showed highly significant correlations with the disease and interplay with one another. Study results show lack of strategies and policies that promote effective prevention and control of Kala-azar. Stakeholders’ analysis revealed limited community awareness regarding roles played by different individuals in Kala-azar prevention, control, and elimination. Conclusions: There is a major gap in cooperation of partners in human, animal, and environmental health for achievements in public health strategies, therefore One Health approach should be adopted for integrated prevention, control, and elimination. The approach will sustainably improve and promote health while addressing the entire spectrum of disease control, including detection, preparedness, response, and management in addition to disease prevention averting this terrible disease from resurfacing in the future.

A review of non-invasive samples and tools in kala-azar diagnosis and test of cure

The recurrence of visceral leishmaniasis (VL), also called kala-azar (KA), in endemic regions of tropical countries like India, is primarily attributed to asymptomatic VL, post-kala azar dermal leishmaniasis (PKDL), and human immunodeficiency virus (HIV) co-infection. To effectively manage VL cases and elimination targets, an early and rapid diagnosis as well as accurate field surveillance is highly essential. The traditional sampling methods like bone marrow (BM), spleen, and lymph node (LN) tissue aspirations are invasive, painful, tedious, and prone to nosocomial infections, require skilled persons and hospital facilities, and are not feasible in rural areas. Therefore, there is an urgent requirement for the adoption of a patient-friendly, non-invasive, non-hospitalized sampling procedure that ensures an effective VL diagnosis. This review aims to meticulously evaluate the most recent scientific research that focuses on the precision, feasibility, and applicability of non-invasive sampling (NIS) and techniques for the diagnosis and test of cure of VL, particularly in resource-limited settings. Apart from that, the non-invasive techniques (NIT) that have shown promising results while monitoring VL treatment response and relapse are also reviewed. The limitations associated with NIT and possible improvements in this regard are discussed as well to improve the diagnosis and management of VL.

Modelling spatiotemporal patterns of visceral leishmaniasis incidence in two endemic states in India using environment, bioclimatic and demographic data, 2013-2022.

As of 2021, the National Kala-azar Elimination Programme (NKAEP) in India has achieved visceral leishmaniasis (VL) elimination (<1 case / 10,000 population/year per block) in 625 of the 633 endemic blocks (subdistricts) in four states. The programme needs to sustain this achievement and target interventions in the remaining blocks to achieve the WHO 2030 target of VL elimination as a public health problem. An effective tool to analyse programme data and predict/ forecast the spatial and temporal trends of VL incidence, elimination threshold, and risk of resurgence will be of use to the programme management at this juncture. We employed spatiotemporal models incorporating environment, climatic and demographic factors as covariates to describe monthly VL cases for 8-years (2013-2020) in 491 and 27 endemic and non-endemic blocks of Bihar and Jharkhand states. We fitted 37 models of spatial, temporal, and spatiotemporal interaction random effects with covariates to monthly VL cases for 6-years (2013-2018, training data) using Bayesian inference via Integrated Nested Laplace Approximation (INLA) approach. The best-fitting model was selected based on deviance information criterion (DIC) and Watanabe-Akaike Information Criterion (WAIC) and was validated with monthly cases for 2019-2020 (test data). The model could describe observed spatial and temporal patterns of VL incidence in the two states having widely differing incidence trajectories, with >93% and 99% coverage probability (proportion of observations falling inside 95% Bayesian credible interval for the predicted number of VL cases per month) during the training and testing periods. PIT (probability integral transform) histograms confirmed consistency between prediction and observation for the test period. Forecasting for 2021-2023 showed that the annual VL incidence is likely to exceed elimination threshold in 16-18 blocks in 4 districts of Jharkhand and 33-38 blocks in 10 districts of Bihar. The risk of VL in non-endemic neighbouring blocks of both Bihar and Jharkhand are less than 0.5 during the training and test periods, and for 2021-2023, the probability that the risk greater than 1 is negligible (P<0.1). Fitted model showed that VL occurrence was positively associated with mean temperature, minimum temperature, enhanced vegetation index, precipitation, and isothermality, and negatively with maximum temperature, land surface temperature, soil moisture and population density. The spatiotemporal model incorporating environmental, bioclimatic, and demographic factors demonstrated that the KAMIS database of the national programmme can be used for block level predictions of long-term spatial and temporal trends in VL incidence and risk of outbreak / resurgence in endemic and non-endemic settings. The database integrated with the modelling framework and a dashboard facility can facilitate such analysis and predictions. This could aid the programme to monitor progress of VL elimination at least one-year ahead, assess risk of resurgence or outbreak in post-elimination settings, and implement timely and targeted interventions or preventive measures so that the NKAEP meet the target of achieving elimination by 2030.

Construction of an evaluation index system for the capability of comprehensive control of mountain - type zoonotic visceral leishmaniasis based on the One Health concept

To construct an evaluation index system for the capability of comprehensive control of mountain-type zoonotic visceral leishmaniasis based on the One Health concept, so as to provide insights into the control and elimination of mountain-type zoonotic visceral leishmaniasis using the One Health approach. A preliminary evaluation index system was constructed based on literature review, panel discussions and field surveys. Thirty-three experts were selected from 7 provincial disease control and prevention centers in Beijing Municipality, Hebei Province, Shanxi Province, Henan Province, Sichuan Province, Shaanxi Province and Gansu Province where mountain-type zoonotic visceral leishmaniasis was endemic, and two rounds of expert consultations were conducted to screen the indicators. The positive coefficient, degree of concentration, degree of coordination, and authority of the experts were calculated, and the normalized weights of each index were calculated with the analytic hierarchy process. The response rates of questionnaires during two rounds of expert consultation were both 100.00% (33/33), and the authority coefficients of the experts were 0.86 and 0.88, respectively. The coefficients of coordination among experts on the rationality, importance, and operability of the indicators were 0.392, 0.437, 0.258, and 0.364, 0.335, 0.263, respectively (all P values < 0.05). Following screening, the final evaluation index system included 3 primary indicators, 17 secondary indicators, and 50 tertiary indicators. The normalized weights of primary indicators "external environment", "internal support" and "comprehensive control" were 16.98%, 38.73% and 44.29%, respectively. Among the secondary indicators of the primary indicator "external environment", the highest weight was seen for natural environment (66.67%), and among the secondary indicators of the primary indicator "internal support", the lowest weight was seen for the scientific research for visceral leishmaniasis control (8.26%), while other indicators had weights of 12.42% to 13.38%. Among the secondary indicators of the primary indicator "comprehensive control", the weight was 16.67% for each indicator. An evaluation index system has been constructed for the capability of comprehensive control of mountain-type zoonotic visceral leishmaniasis based on the One Health concept. In addition to assessment of the effect of conventional mountain-type zoonotic visceral leishmaniasis control measures, this index system integrates the importance of top-level design, organizational management, and implementation of control measures, and includes indicators related to multi-sectoral cooperation.

Molecular monitoring of treatment efficacy in human visceral leishmaniasis.

Focused efforts of the visceral leishmaniasis elimination program have led to a drastic decline in cases, and the present challenge is disease monitoring, which this study aimed to assess. A Leishmania kinetoplastid-targeted qPCR quantified parasite load at disease presentation, and following treatment completion (n=49); an additional 80 cases were monitored after completion of treatment. The parasite load at disease presentation was 13 461.00 (2560.00-37764.00)/µg gDNA, which upon completion of treatment reduced in 47 of 49 cases to 1(1-1)/µg gDNA, p<0.0001. In 80 cases that presented >2 months post-treatment, their parasite burden similarly decreased to 1(1-1)/µg gDNA except in 6 of 80 cases, which were qPCR positive. In 129 cases of visceral leishmaniasis, qPCR by quantification of parasite burden proved effective for monitoring treatment.

Epidemiological, Serological, and Entomological Investigation of New Visceral Leishmaniasis Foci in Nepal.

The aim of this study was to explore epidemiological, serological, entomological, and social aspects of visceral leishmaniasis (VL) in new foci in Nepal. The study was conducted in 11 villages of five districts that had been previously free of VL but that reported new cases between 2019 and 2021. We screened 1,288 inhabitants using rK39 tests and investigated the epidemiological and clinical characteristics of 12 recent VL cases. A total of 182 community members were interviewed about knowledge, attitude, and practices regarding VL. They then underwent an awareness training; 40 of them had a second interview at 6 months to assess the training impact. Vector surveys were conducted in six houses per village to assess sandfly density and infection rates. The prevalence of VL infection was 0.5% and 3.2% among screened populations in Dolpa and Kavre districts, respectively, while the other districts had no rK39-positive cases. No association between travel history and VL infection was found. Phlebotomus argentipes sandflies were collected in three districts at high altitudes (from 1,084 to 4,450 m). None of the sandflies captured had Leishmania donovani DNA. People in new foci were not aware of VL symptoms, vectors, or preventive measures. The training significantly improved their knowledge and practice in seeking medical care in case of illness. The epidemiological, serological, and entomological investigations suggest indigenous focal transmission of VL. An integrated package of strategic interventions should be implemented by the national VL elimination program in districts with new VL foci.

A mathematical model of visceral leishmaniasis transmission and control: Impact of ITNs on VL prevention and elimination in the Indian subcontinent.

Visceral Leishmaniasis (VL) is a deadly, vector-borne, parasitic, neglected tropical disease, particularly prevalent on the Indian subcontinent. Sleeping under the long-lasting insecticide-treated nets (ITNs) was considered an effective VL prevention and control measures, until KalaNet, a large trial in Nepal and India, did not show enough supporting evidence. In this paper, we adapt a biologically accurate, yet relatively simple compartmental ordinary differential equations (ODE) model of VL transmission and explicitly model the use of ITNs and their role in VL prevention and elimination. We also include a game-theoretic analysis in order to determine an optimal use of ITNs from the individuals' perspective. In agreement with the previous more detailed and complex model, we show that the ITNs coverage amongst the susceptible population has to be unrealistically high (over 96%) in order for VL to be eliminated. However, we also show that if the whole population, including symptomatic and asymptomatic VL cases adopt about 90% ITN usage, then VL can be eliminated. Our model also suggests that ITN usage should be accompanied with other interventions such as vector control.

Visceral leishmaniasis in the hills of western Nepal: A transmission assessment.

In Nepal, visceral leishmaniasis (VL) has been targeted for elimination as a public health problem by 2026. Recently, increasing numbers of VL cases have been reported from districts of doubtful endemicity including hills and mountains, threatening the ongoing VL elimination program in Nepal. We conducted a multi-disciplinary, descriptive cross-sectional survey to assess the local transmission of Leishmania donovani in seven such districts situated at altitudes of up to 1,764 meters in western Nepal from March to December 2019. House-to-house surveys were performed for socio-demographic data and data on past and current VL cases. Venous blood was collected from all consenting individuals aged ≥2 years and tested with the rK39 RDT. Blood samples were also tested with direct agglutination test, and a titer of ≥1:1600 was taken as a marker of infection. A Leishmania donovani species-specific PCR (SSU-rDNA) was performed for parasite species confirmation. We also captured sand flies using CDC light traps and mouth aspirators. The house-to-house surveys documented 28 past and six new VL cases of which 82% (28/34) were without travel exposure. Overall, 4.1% (54/1320) of healthy participants tested positive for L. donovani on at least one serological or molecular test. Among asymptomatic individuals, 17% (9/54) were household contacts of past VL cases, compared to 0.5% (6/1266) among non-infected individuals. Phlebotomus argentipes, the vector of L. donovani, was found in all districts except in Bajura. L. donovani was confirmed in two asymptomatic individuals and one pool of sand flies of Phlebotomus (Adlerius) sp. We found epidemiological and entomological evidence for local transmission of L. donovani in areas previously considered as non-endemic for VL. The national VL elimination program should revise the endemicity status of these districts and extend surveillance and control activities to curb further transmission of the disease.