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Visceral leishmaniasis is a serious public health problem on the Indian subcontinent, causing high morbidity and mortality. The governments in the region launched a visceral leishmaniasis elimination initiative in 2005. We review knowledge gaps and research priorities. Key challenges include low coverage of health services for those most at risk, drug resistance, the absence of a vaccine, and the complex biology of the sandfly–human host transmission cycle. Vector control is an essential component, but innovation in this field is insufficient. Substantial progress has been made in the area of diagnostic, therapeutic, and vaccine development, but there are still many hurdles to overcome. For visceral leishmaniasis elimination to become a reality, effective deployment of these existing and new tools is essential. A strong commitment at community level is imperative, and appropriate diagnostic and treatment services as well as effective epidemiological surveillance need to be ensured.

Background Cutaneous Leishmaniasis (CL) is a parasitic skin disease, linked to poverty, and belonging to the group of Neglected Tropical Diseases. Depending on the severity, the type of lesions or scars, and the context, CL can lead to self- and social stigma influencing the quality of life and psychological well-being of the patient. This dimension is, however, little documented for the most common, localized form of cutaneous leishmaniasis (LCL). We aimed to describe the current knowledge on the psychological burden and the stigma related to LCL. Methods The population of interest for this scoping review are patients or their relatives with localized LCL or related scars. We searched the electronic databases PubMed, Web of Knowledge, PsycINFO, POPLINE, Cochrane Library, Science Direct, Global Health, and LILACS, for articles written in Arabic, English, French, Dutch, Portuguese, or Spanish, and published until the end of August 2017. Results From 2485 initial records, 15 papers met our inclusion criteria. Dermatology life quality index was the most frequent used scale to assess LCL psychological impact in quantitative studies. Six qualitative studies used individual interviews and/or focus groups discussions to explore the psychological and/or the social burden of this disease. Quantitative assessments using standard scales as well as qualitative research asserts that LCL is a source of psychological suffering, stigmatization, and decreased quality of life (QoL). Conclusion Most studies showed that LCL has a significant negative effect on the QoL and mental health. However, the fact that the psychosocial burden generated by LCL is time-dependent makes it hard to measure. We recommend to develop a more specific and validated assessment scale to appreciate the full burden of this disease and enhance comparability of findings.

To document the psychosocial burden of Cutaneous Leishmaniasis (CL) in rural communities in Southeastern Morocco. Between March and April 2015, we conducted qualitative research in communities exposed to Leishmania major or L. tropica in Errachidia and Tinghir provinces. Twenty-eight focus groups discussions (FGDs) were realized, with a stratification by gender and tradition of medicine (users of folk versus professional medicine). Data were analyzed using content analysis. This rural population most exposed to CL in Morocco lacks access to health care in general and clearly points out there are other major public health issues that need to be resolved. Nonetheless, respondents consider the impact of CL lesions and scars as important and similar to that of burn scar tissue. Young women with CL scars in the face are stigmatized and will often be rejected for marriage in these communities. People usually try a long list of folk remedies on the active lesions, but none was felt adequate. There was a clear demand for better treatment as well as for treatment of the scars. The psycho-social impact of CL due to L.major and L.tropica is substantial, especially for young single women with facial scars. These generate social and self-stigma and diminish their marriage prospects. CL is well known, but not considered as a major health priority by these poor rural communities in South-eastern Morocco where gender discrimination is still an issue and access to basic health care is as neglected as CL. Early CL diagnosis and new treatment options with better skin outcomes are urgently needed.

Combination therapy for the treatment of visceral leishmaniasis has increasingly been advocated as a way to increase treatment efficacy and tolerance, reduce treatment duration and cost, and limit the emergence of drug resistance. We reviewed the evidence and potential for combination therapy, and the criteria for the choice of drugs in such regimens. The first phase 2 results of combination regimens are promising, and have identified effective and safe regimens as short as 8 days. Several phase 3 trials are underway or planned in the Indian subcontinent and east Africa. The limited data available suggest that combination therapy is more cost-effective and reduces indirect costs for patients. Additional advantages are reduced treatment duration (8–17 days), with potentially better patient compliance and lesser burden on the health system. Only limited data are available on how best to prevent acquired resistance. Patients who are coinfected with visceral leishmaniasis and HIV could be a reservoir for development and spread of drug-resistant strains, calling for special precautions. The identification of a short, cheap, well-tolerated combination regimen that can be given in ambulatory care and needs minimal clinical monitoring will most likely have important public health implications. Effective monitoring systems and close regulations and policy will be needed to ensure effective implementation. Whether combination therapy could indeed help delay resistance, and how this is best achieved, will only be known in the long term.

Every year there are an estimated 500,000 new cases of visceral leishmaniasis (VL) and more than 50,000 deaths from the disease, a death toll that is surpassed among the parasitic diseases only by malaria. The epidemiology, clinical presentation and pathogenesis of VL are reviewed, along with the current control strategies and research challenges. Visceral leishmaniasis (VL) is a systemic protozoan disease that is transmitted by phlebotomine sandflies. Poor and neglected populations in East Africa and the Indian sub-continent are particularly affected. Early and accurate diagnosis and treatment remain key components of VL control. In addition to improved diagnostic tests, accurate and simple tests are needed to identify treatment failures. Miltefosine, paromomycin and liposomal amphotericin B are gradually replacing pentavalent antimonials and conventional amphotericin B as the preferred treatments in some regions, but in other areas these drugs are still being evaluated in both mono- and combination therapies. New diagnostic tools and new treatment strategies will only have an impact if they are made widely available to patients.

Visceral leishmaniasis (VL) remains an important public health issue worldwide causing substantial morbidity and mortality. The Indian subcontinent accounted for up to 90% of the global VL burden in the past but made significant progress during recent years and is now moving towards elimination. However, to achieve and sustain elimination of VL, knowledge gaps on infection reservoirs and transmission need to be addressed urgently. Xenodiagnosis is the most direct way for testing the infectiousness of hosts to the vectors and can be used to investigate the dynamics and epidemiology of Leishmania donovani transmission. There are, however, several logistic and ethical issues with xenodiagnosis that need to be addressed before its application on human subjects. In the current Review, we discuss the critical knowledge gaps in VL transmission and the role of xenodiagnosis in disease transmission dynamics along with its technical challenges. Establishment of state of the art xenodiagnosis facilities is essential for the generation of much needed evidence in the VL elimination initiative.

Visceral Leishmaniasis (VL) is an important protozoan opportunistic disease in HIV patients in endemic areas. East Africa is second to the Indian subcontinent in the global VL caseload and first in VL-HIV coinfection rate. Because of the alteration in the disease course, the diagnostic challenges, and the poor treatment responses, VL with HIV coinfection has become a very serious challenge in East Africa today. Field experience with the use of liposomal amphotericin B in combination with miltefosine, followed by secondary prophylaxis and antiretroviral drugs, looks promising. However, this needs to be confirmed through clinical trials. Better diagnostic and follow-up methods for relapse and prediction of relapse should also be looked for. Basic research to understand the immunological interaction of the two infections may ultimately help to improve the management of the coinfection.

Despite the overall decrease in visceral leishmaniasis (VL) incidence on the Indian subcontinent, there remain spatiotemporal clusters or 'hotspots' of new cases. The characteristics of these hotspots, underlying transmission dynamics, and their importance for shaping control strategies are not yet fully understood and are investigated in this study for a VL endemic area of ~100,000 inhabitants in Bihar, India between 2007-2015. VL incidence (cases/10,000/year) dropped from 12.3 in 2007 to 0.9 in 2015, which is just below the World Health Organizations' threshold for elimination as a public health problem. Clustering of VL was assessed between subvillages (hamlets), using multiple geospatial and (spatio)temporal autocorrelation and hotspot analyses. One to three hotspots were identified each year, often persisting for 1-5 successive years with a modal radius of ~500m. The relative risk of having VL was 5-86 times higher for inhabitants of hotspots, compared to those living outside hotspots. Hotspots harbour significantly more households from the two lowest asset quintiles (as proxy for socio-economic status). Overall, children and young adelescents (5-14 years) have the highest risk for VL, but within hotspots and at the start of outbreaks, older age groups (35+ years) show a comparable high risk. This study demonstrates significant spatiotemporal heterogeneity in VL incidence at subdistrict level. The association between poverty and hotspots confirms that VL is a disease of 'the poorest of the poor' and age patterns suggest a potential role of waning immunity as underlying driver of hotspots. The recommended insecticide spraying radius of 500m around detected VL cases corresponds to the modal hotspot radius found in this study. Additional data on immunity and asymptomatic infection, and the development of spatiotemporally explicit transmission models that simulate hotspot dynamics and predict the impact of interventions at the smaller geographical scale will be crucial tools in sustaining elimination.

As Bangladesh, India and Nepal progress towards visceral leishmaniasis (VL) elimination, it is important to understand the role of asymptomatic Leishmania infection (ALI), VL treatment relapse and post kala-azar dermal leishmaniasis (PKDL) in transmission. We reviewed evidence systematically on ALI, relapse and PKDL. We searched multiple databases to include studies on burden, risk factors, biomarkers, natural history, and infectiveness of ALI, PKDL and relapse. After screening 292 papers, 98 were included covering the years 1942 through 2016. ALI, PKDL and relapse studies lacked a reference standard and appropriate biomarker. The prevalence of ALI was 4-17-fold that of VL. The risk of ALI was higher in VL case contacts. Most infections remained asymptomatic or resolved spontaneously. The proportion of ALI that progressed to VL disease within a year was 1.5-23%, and was higher amongst those with high antibody titres. The natural history of PKDL showed variability; 3.8-28.6% had no past history of VL treatment. The infectiveness of PKDL was 32-53%. The risk of VL relapse was higher with HIV co-infection. Modelling studies predicted a range of scenarios. One model predicted VL elimination was unlikely in the long term with early diagnosis. Another model estimated that ALI contributed to 82% of the overall transmission, VL to 10% and PKDL to 8%. Another model predicted that VL cases were the main driver for transmission. Different models predicted VL elimination if the sandfly density was reduced by 67% by killing the sandfly or by 79% by reducing their breeding sites, or with 4-6y of optimal IRS or 10y of sub-optimal IRS and only in low endemic setting. There is a need for xenodiagnostic and longitudinal studies to understand the potential of ALI and PKDL as reservoirs of infection.

While three countries in South Asia decided to eliminate anthroponotic visceral leishmaniasis (VL) by 2015, its control in other regions seems fraught with difficulties. Is there a scope for more effective VL control in the Americas where transmission is zoonotic? We reviewed the evidence on VL control strategies in Latin America-diagnosis, treatment, veterinary interventions, vector control-with respect to entomological and clinical outcomes. We searched the electronic databases of MEDLINE, LILACS, and the Cochrane Central Register of Controlled Trials, from 1960 to November 2008 and references of selected articles. Intervention trials as well as observational studies that evaluated control strategies of VL in the Americas were included. While the use of rapid diagnostic tests for VL diagnosis seems well established, there is a striking lack of evidence from clinical trials for drug therapy and few well designed intervention studies for control of vectors or canine reservoirs. Elimination of zoonotic VL in the Americas does not seem a realistic goal at this point given the lack of political commitment, gaps in scientific knowledge, and the weakness of case management and surveillance systems. Research priorities and current strategies should be reviewed with the aim of achieving better VL control.