• Leishmania donovani
• Kenya
• Spatiotemporal analysis
• Visceral leishmaniasis

• Humans
• Leishmaniasis, Visceral/epidemiology
• Kenya/epidemiology
• Spatio-Temporal Analysis
• Female
• Male
• Incidence
• Adult
• Child
• Adolescent
• Young Adult
• Child, Preschool
• Disease Outbreaks
• Seasons
• Infant
• Middle Aged
• Hospitalization/statistics & numerical data

• Work Visit Grant 2022 Amsterdam Institute for Immunology and Infectious Diseases

• Kenya
• case–control study
• risk factors
• sandfly
• visceral leishmaniasis

• Leishmaniasis, Visceral/epidemiology
• Leishmaniasis, Visceral/transmission
• Humans
• Kenya/epidemiology
• Case-Control Studies
• Risk Factors
• Male
• Female
• Adult
• Animals
• Child
• Adolescent
• Young Adult
• Child, Preschool
• Middle Aged
• Dogs
• Housing
• Surveys and Questionnaires

• Amsterdam Institute for Immunology and Infectious Diseases

• Phlebotomus orientalis
• cattle
• control
• host preference
• human blood index
• livestock
• sand flies
• visceral leishmaniasis

• Female
• Humans
• Animals
• Cattle
• Sheep
• Phlebotomus
• Leishmaniasis, Visceral/veterinary
• Psychodidae
• Sudan/epidemiology
• Equidae
• Goats
• Cattle Diseases
• Goat Diseases
• Sheep Diseases

• Humans
• Animals
• Cattle
• Mosquito Vectors
• Animals, Wild
• Vector Borne Diseases/epidemiology
• Vector Borne Diseases/prevention & control
• Pest Control
• Insecticides

• National Institute of Food and Agriculture
• Sharon Gray Memorial Award; School of Integrative Biology; UIUC

Leishmaniasis is a vector-borne parasitic disease affecting millions of people worldwide. However, in the last decade, the number of cases has been reduced from well-documented endemic parts, but sporadic cases have been reported widely from various non-endemic areas, especially from the southern Himalayan zone. This raises concerns about the emergence of new ecological niches. This warrants a critical evaluation of key factors causing this rapid spread and possibly indigenous transmission. This mini-review article is aimed to briefly address the parasite, the vector, and the environmental aspects in the transmission of leishmaniasis in these new foci against a background of worldwide endemic leishmaniasis with a special focus on the southern Himalayan zone. As the lack of knowledge about the causative parasites, vectors, reservoir hosts, atypical presentations, and their management make the problem serious and may lead to the emergence of public health issues. The present works also reviewed the existing information regarding clinical variations, diagnostic methods, treatment, its outcome, and ignite for further research in these aspects of the disease.

• Anthroponosis
• Kala azar sandfly
• Sporadic transmission
• Southern Himalaya

• diagnosis methods
• drug resistance
• parasite identification
• visceral leishmaniasis

• Animals
• Anti-Bacterial Agents/administration & dosage
• Antibiotic Prophylaxis
• Bacteria/classification
• Bacteria/genetics
• Bacteria/isolation & purification
• Bacterial Infections/prevention & control
• Bacterial Physiological Phenomena
• Coinfection/microbiology
• Coinfection/prevention & control
• Cricetinae
• Disease Progression
• Female
• Gastrointestinal Microbiome
• Humans
• Intestinal Diseases, Parasitic/parasitology
• Leishmania donovani/physiology
• Leishmaniasis, Visceral/complications
• Leishmaniasis, Visceral/parasitology
• Male
• Mesocricetus
• Mice
• Mice, Inbred C57BL
• Symbiosis

• MR/R021430/1 Medical Research Council
• Division of Intramural Research, National Institute of Allergy and Infectious Diseases
• FP7 People: Marie-Curie Actions

Visceral leishmaniasis (VL, also called kala-azar) is a public health problem in Ethiopia, especially in sesame and sorghum growing areas. Compared to other populations, labor migrants are the most exposed. Knowing the seroprevalence of Leishmania donovani and associated risk factors is essential to design appropriate control measures. The main aim of this study was to assess the seroprevalence of asymptomatic L. donovani among laborers and associated risk factors in agricultural camps of West Armachiho district, Northwest Ethiopia. Therefore, this study was conducted to know the seroprevalence and associated risk factors of L. donovani infection.

A cross-sectional study was conducted among 185 laborers from October to December 2017. A simple random sampling technique was used to select study participants from selected agricultural camps. After obtaining written informed consent, data were collected using a structured pretested Amharic version questionnaire using the interview technique. A single finger prick blood sample was collected from the study participants and the blood samples were subjected to the serological diagnostic method using the rk39 kit. The multivariable logistic regression model was used to identify risk factors associated with L. donovani infection.

Among 185 participants examined using rk39, 14 (7.6%) were seroreactive for L. donovani. Leishmania donovani infection had a statistically significant association with sleeping under Balanites trees (AOR: 4.36, 95%CI: 1.186-16.06), presence of domestic animals near sleeping place (AOR: 4.68, 95% CI: 1.25-17.56), and lack of knowledge about VL transmission (AOR: 3.79, 95% CI: 1.07-13.47).

Seroprevalence of asymptomatic L. donovani among laborers in agricultural camps of West Armachiho was low. Prevention measures and health education about risk factors that expose to L. donovani infection for the laborers are essential to prevent the spread of the disease.

Visceral Leishmaniasis (VL) is endemic to the Attica region of Greece. The geographical distribution of VL cases was analyzed employing methods of spatial analysis in a GIS environment. A geographic database was constructed including data for the disease cases and environmental factors, such as land cover types, stray dog population, and socioeconomic factors. Classic and spatial regression models are presented that suggest the factors contributing most to the incidence of leishmaniasis are green urban areas and the population of stray dogs in the municipalities of Attica region. The results of the spatial regression model were more accurate, thus were used to produce a disease risk map. This map indicates the high-risk municipalities in which surveillance for the control of leishmaniasis is necessary.

• Greece
• geographic information systems
• spatial regression
• visceral leishmaniasis

Early diagnosis and treatment is the principal strategy to control visceral leishmaniasis (VL), or kala-azar in East Africa. As VL strikes remote rural, sparsely populated areas, kala-azar care might not be accessed optimally or timely. We conducted a qualitative study to explore access barriers in a longstanding kala-azar endemic area in southern Gadarif, Sudan. Former kala-azar patients or caretakers, community leaders, and health-care providers were purposively sampled and thematic data analysis was used. Our study participants revealed the multitude of difficulties faced when seeking care. The disease is well known in the area, yet misconceptions about causes and transmission persist. The care-seeking itineraries were not always straightforward: “shopping around” for treatments are common, partly linked to difficulties in diagnosing kala-azar. Kala-azar is perceived to be “hiding,” requiring multiple tests and other diseases must be treated first. Negative perceptions on quality of care in the public hospitals prevail, with the unavailability of drugs or staff as the main concern. Delay to seek care remains predominantly linked to economic constraint: albeit treatment is for free, patients have to pay out of pocket for everything else, pushing families further into poverty. Despite increased efforts to tackle the disease over the years, access to quality kala-azar care in this rural Sudanese context remains problematic. The barriers explored in this study are a compelling reminder of the need to boost efforts to address these barriers.

The 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.

• Leishmaniasis
• animal models
• cytokines
• patient follow-up
• skin lesions
• virulence

Quantitation of the nonlinear heterogeneities in Leishmania parasites, sand fly vectors, and mammalian host relationships provides insights to better understand leishmanial transmission epidemiology towards improving its control. The parasite manipulates the sand fly via production of promastigote secretory gel (PSG), leading to the “blocked sand fly” phenotype, persistent feeding attempts, and feeding on multiple hosts. PSG is injected into the mammalian host with the parasite and promotes the establishment of infection. Animal models demonstrate that sand flies with the highest parasite loads and percent metacyclic promastigotes transmit more parasites with greater frequency, resulting in higher load infections that are more likely to be both symptomatic and efficient reservoirs. The existence of mammalian and sand fly “super-spreaders” provides a biological basis for the spatial and temporal clustering of clinical leishmanial disease. Sand fly blood-feeding behavior will determine the efficacies of indoor residual spraying, topical insecticides, and bed nets. Interventions need to have sufficient coverage to include transmission hot spots, especially in the absence of field tools to assess infectiousness. Interventions that reduce sand fly densities in the absence of elimination could have negative consequences, for example, by interfering with partial immunity conferred by exposure to sand fly saliva. A deeper understanding of both sand fly and host biology and behavior is essential to ensuring effectiveness of vector interventions.

We review recent research that sheds light on the quantitative biology of leishmanial transmission between sand flies and mammalian hosts and use these insights to better understand transmission, the observed epidemiology of the disease, and their implications in choice of control strategy. Using animal models, we show how the parasite-induced processes manipulate sand fly blood-feeding behavior and the infectious metacyclic dose to promote host infection and to differentially regulate the onward transmission potential of individual vectors and hosts. The existence of subpopulations of mammalian and sand fly “super-spreaders” provides a biological basis for the spatial and temporal clustering of clinical leishmanial disease. While tools are unavailable to distinguish these individuals in mixed populations, blanket interventions will be necessary to ensure inclusion of transmission hot spots. Interventions that reduce sand fly densities without elimination could interfere with vector—host dynamics and conferred partial immunity to host populations.

• Animals
• Host-Pathogen Interactions/immunology
• Humans
• Insect Vectors/parasitology
• Leishmania/parasitology
• Leishmaniasis/epidemiology
• Leishmaniasis/parasitology
• Leishmaniasis/transmission
• Parasites/parasitology
• Parasites/pathogenicity
• Psychodidae/parasitology

• Wellcome Trust
• BB/H022406/1 Biotechnology and Biological Sciences Research Council

• AGMO
• Kala-azar relapse
• exome sequencing
• genetic variants
• haploinsufficiency

• Health Services Accessibility
• Humans
• Leishmaniasis, Visceral/diagnosis
• Leishmaniasis, Visceral/drug therapy
• Leishmaniasis, Visceral/epidemiology
• Somalia/epidemiology

• Animals
• Cytokines/immunology
• Female
• Humans
• Immunotherapy
• Interleukin-10/immunology
• Leishmania donovani/physiology
• Leishmaniasis, Visceral/immunology
• Leishmaniasis, Visceral/parasitology
• Leishmaniasis, Visceral/therapy
• Mice
• Mice, Inbred C57BL
• Spleen/immunology
• Spleen/parasitology
• Th1 Cells/immunology

• P50 AI074321 NIAID NIH HHS
• U19 AI074321 NIAID NIH HHS
• 2P50AI074321 NIAID NIH HHS

• Trypanotolerance
• asymptomatic
• elimination
• leishmaniasis
• trypanosomatids
• trypanosomiasis

• Adolescent
• Adult
• Age Factors
• Aged
• Aged, 80 and over
• Animals
• Case-Control Studies
• Child
• Child, Preschool
• Environmental Exposure
• Female
• Humans
• Infant
• Infant, Newborn
• Leishmaniasis, Visceral/epidemiology
• Male
• Middle Aged
• Rural Population
• Sex Factors
• Sudan/epidemiology
• Surveys and Questionnaires
• Young Adult

Leishmaniasis is a vector-borne disease caused by protozoan parasites of the genus Leishmania. It is transmitted by phlebotomine female sand flies of the genera Phlebotomus and Lutzomyia in the old and new world, respectively. More than 20 well-recognized Leishmania species are known to infect humans and cause visceral (VL), cutaneous (CL) and mucocutaneous (ML) forms of the disease. Approximately 350 million people are at risk of contracting the disease and an estimated 1.6 million new cases occur annually. The disease mainly affects poor people in Africa, Asia and Latin America, and is associated with malnutrition, population migration, poor residency conditions, frail immune system and lack of resources. Previously, diagnosis of leishmaniasis relied mainly on invasive techniques of detecting parasites in splenic and bone marrow aspirates. Nevertheless, serological tests using the recombinant kinesin antigen (rK39) and molecular methods (polymerase chain reaction) are considered the best options for diagnosis today, despite problems related to varying sensitivities and specificities and field adaptability. Therapy of leishmaniasis ranges from local treatment of cutaneous lesions to systemic often toxic, therapy for disseminated CL, ML and VL. Agents with efficacy against leishmaniasis include amphotericin B, pentavalent antimonial drugs, paromomycin and miltefosine. No single therapy of VL currently offers satisfactory efficacy along with safety. This article provides a brief and updated systematic review on the epidemiology, diagnosis and treatment of this neglected disease.

• Cutaneous
• diagnosis
• epidemiology
• leishmaniasis
• treatment
• visceral

Visceral leishmaniasis (VL) or kala-azar cases in seasonal labour migrants from highland areas are addressed to travel history to the Metema–Humera lowlands, northwestern Ethiopia. Factors that affect the incidence of VL in extra-domestic habitats were not evaluated. The aim of this study was to evaluate sero-prevalence of Leishmania donovani infection in randomly selected labour migrant workers and entomological risk factors which might affect the incidence of kala-azar.

Sero-prevalence of L. donovani infection in labour migrants was obtained from Direct Agglutination Test (DAT) using blood samples. Logistic regression analysis was used to correlate the possible risk factors with L. donovani infection. The season for L. donovani infection or Phlebotomus orientalis bite was estimated from the study of population dynamic of P. orientalis in areas where the blood was sampled.

A total of 7, 443 P. orientalis (1,748 female and 5,695 male) were collected from agricultural fields and thickets of Acacia seyal using 461 CDC light traps. The highest mean number of P. orientalis/trap in the thickets of A. seyal and agricultural fields were 46.9 and 43.9 in March and April respectively. The mean P. orientalis/trap for November – May dry season in agricultural fields (11.39) and thickets of A. seyal (25.30) were higher compared to 0.66 in fields and 3.92 in thickets during June – August weeding season. Of the total 359 labour migrants screened using DAT, 45 (12.5%) were DAT-positive (≥1:800) for L. donovani infections. Very high titers (1:12800) were found in 3 (0.8%) individuals who had the risk of kala-azar development. Statistically significant p-values and odd ratio (OR) for staying in the areas both in the weeding and harvesting seasons (p = 0.035; OR = 2.83) and sleeping in the agricultural fields (p = 0.01; OR = 15.096) were positively correlated with L. donovani infection. Night harvest (p = 0.028; OR = 0.133) and knowledge about sign or symptoms (p = 0.042; OR = 0.383) were negatively associated with this infection.

Sleeping in open agricultural fields was related with L. donovani infections in labour migrants during June-August weeding season.

• Leishmania
• aneuploidy.
• mix mating
• population genetic
• sex

• Arab world
• Bibliometric
• Infectious diseases
• Web of science

• Leishmaniasis
• Uganda
• management

• Antiprotozoal Agents/therapeutic use
• Humans
• Leishmaniasis, Visceral/drug therapy
• Leishmaniasis, Visceral/epidemiology
• Population Surveillance
• Risk Factors
• Uganda/epidemiology

• asymptomatic infection
• immunity
• visceral leishmaniasis

• Adolescent
• Adult
• Aged
• Antibodies, Protozoan/blood
• Antigens, Protozoan/immunology
• Child
• Child, Preschool
• Chromatography, Affinity
• Female
• Humans
• Immunoglobulin G/blood
• India/epidemiology
• Infant
• Leishmania donovani/immunology
• Leishmaniasis, Visceral/diagnosis
• Leishmaniasis, Visceral/epidemiology
• Leishmaniasis, Visceral/immunology
• Male
• Middle Aged
• Sudan/epidemiology
• Young Adult

There is increasing interest in the role of asymptomatic infection in transmission of Visceral Leishmaniasis (VL). We studied the individual, household and environmental factors associated with asymptomatic Leishmania donovani infected individuals and VL. 7,538 individuals living in VL endemic villages in India and Nepal were divided into three mutually exclusive groups based on their VL history and Direct Agglutination Test (DAT) results in yearly serosurveys over a two-year period. The groups were (1) VL cases, (2) asymptomatically infected individuals (seroconverters) and (3) seronegative individuals. VL cases and seroconverters were compared to seronegative individuals in mixed logistic regression models. The risk of seroconversion and disease was significantly increased in individuals aged 14 to 24 years old and by the presence of other DAT-positive, asymptomatically infected individuals and VL cases in the house. The risk of seroconversion was higher in Indian than in Nepalese villages and it increased significantly with age, but not so for VL. This study demonstrates that, when risk factors for leishmanial infection and VL disease are evaluated in the same population, epidemiological determinants for asymptomatic infection and VL are largely similar.

• Adolescent
• Adult
• Child
• Child, Preschool
• Female
• Follow-Up Studies
• Humans
• India/epidemiology
• Infant
• Infant, Newborn
• Leishmania donovani
• Leishmaniasis, Visceral/blood
• Leishmaniasis, Visceral/epidemiology
• Leishmaniasis, Visceral/immunology
• Male
• Models, Biological
• Nepal/epidemiology
• Risk Factors

Visceral leishmaniasis is a lethal parasitic disease transmitted by phlebotomine sand flies. The largest focus of VL in Ethiopia is located in the lowland region bordering Sudan, where the epidemiology is complicated by the presence of thousands of seasonal agricultural workers who live under precarious conditions.

We conducted two parallel case-control studies to identify factors associated with VL risk in residents and migrants. The studies were conducted from 2009 to 2011 and included 151 resident cases and 157 migrant cases, with 2 matched controls per case. In multivariable conditional regression models, sleeping under an acacia tree at night (odds ratios (OR) 5.2 [95% confidence interval 1.7–16.4] for residents and 4.7 [1.9–12.0] for migrants), indicators of poverty and lower educational status were associated with increased risk in both populations. Strong protective effects were observed for bed net use (OR 0.24 [0.12–0.48] for net use in the rainy season among residents, OR 0.20 [0.10–0.42] for any net use among migrants). For residents, living in a house with thatch walls conferred 5-fold and sleeping on the ground 3-fold increased risk. Among migrants, the risk associated with HIV status was borderline significant and sleeping near dogs was associated with 7-fold increased risk.

Preventive strategies should focus on ways to ensure net usage, especially among migrant workers without fixed shelters. More research is needed to understand migration patterns of seasonal labourers and vector bionomics.

Visceral leishmaniasis is a lethal parasitic disease transmitted by sand flies. The largest focus of VL in Ethiopia is located in the lowland region bordering Sudan, where hundreds of thousands of agricultural workers migrate for work every year during the planting and harvest seasons. We conducted two parallel studies in residents and migrants to determine the living conditions and behaviors that put people at higher risk of VL risk. We found that sleeping under an acacia tree at night, indicators of poverty and lower educational status were associated with increased risk in both populations. Sleeping under a bed net was protective. For residents, living in a house with thatch walls and sleeping on the ground increased risk of VL. Among migrants, the risk associated with HIV status was borderline significant and sleeping near dogs was associated with increased risk. Preventive strategies should focus on ways to ensure net usage, especially among migrant workers without fixed shelters. More research is needed to understand migration patterns of seasonal labourers and vector behavior.

• Case-Control Studies
• Ethiopia/epidemiology
• Humans
• Leishmaniasis, Visceral/epidemiology
• Risk Factors

• Ecology
• Evolution
• Host–parasite interactions
• Human biology
• Pathogens

• Brazil
• Electrophoresis, Agar Gel
• Gene Frequency
• Genetic Predisposition to Disease/genetics
• Genome-Wide Association Study
• Genotype
• HLA-DQ alpha-Chains/genetics
• HLA-DRB1 Chains/genetics
• Haplotypes/genetics
• Humans
• India
• Leishmaniasis, Visceral/genetics
• Linear Models
• Odds Ratio
• Oligonucleotide Array Sequence Analysis
• Polymorphism, Single Nucleotide/genetics

• 087436/Z/10/Z Wellcome Trust
• P50 AI-30639 NIAID NIH HHS
• P50 AI074321 NIAID NIH HHS
• 095552 Wellcome Trust
• R01 AI048822 NIAID NIH HHS
• 085475/B/08/Z Wellcome Trust
• 085475 Wellcome Trust
• 089698 Wellcome Trust
• 075491/Z/04/B Wellcome Trust
• 074196 Wellcome Trust
• 090532 Wellcome Trust
• Wellcome Trust
• 087436 Wellcome Trust
• P50 AI030639 NIAID NIH HHS
• 097364/Z/11/Z Wellcome Trust
• U19 AI074321 NIAID NIH HHS
• 083948 Wellcome Trust
• 084694 Wellcome Trust
• 074196/Z/04/Z Wellcome Trust
• MC_G1000735 Medical Research Council
• P50AI074321 NIAID NIH HHS
• R01 AI076233 NIAID NIH HHS
• 090532/Z/09/Z Wellcome Trust
• 4584 Cancer Research UK
• 085475/Z/08/Z Wellcome Trust

Since December 2009, Médecins Sans Frontières has diagnosed and treated patients with visceral leishmaniasis (VL) in Tabarak Allah Hospital, eastern Gedaref State, one of the main endemic foci of VL in Sudan. A survey was conducted to estimate the VL incidence in villages around Tabarak Allah.

Between the 5^th of May and the 17^th of June 2011, we conducted an exhaustive door-to-door survey in 45 villages of Al-Gureisha locality. Deaths were investigated by verbal autopsies. All individuals with (i) fever of at least two weeks, (ii) VL diagnosed and treated in the previous year, and (iii) clinical suspicion of post-kala-azar dermal leishmaniasis (PKDL) were referred to medical teams for case ascertainment. A new case of VL was a clinical suspect with a positive rk39 rapid test or direct agglutination test (DAT).

In the 45 villages screened, 17,702 households were interviewed, for a population of 94,369 inhabitants. The crude mortality rate over the mean recall period of 409 days was 0.13/10'000 people per day. VL was a possible or probable cause for 19% of all deaths. The VL-specific mortality rate was estimated at 0.9/1000 per year.

The medical teams examined 551 individuals referred for a history of fever of at least two weeks. Out of these, 16 were diagnosed with primary VL. The overall incidence of VL over the past year was 7.0/1000 persons per year, or 7.9/1000 per year when deaths possibly or probably due to VL were included. Overall, 12.5% (11,943/95,609) of the population reported a past VL treatment episode.

VL represents a significant health burden in eastern Gedaref State. Active VL case detection had a very low yield in this specific setting with adequate access to care and may not be the priority intervention to enhance control in similar contexts.

Visceral leishmaniasis (VL) is a life-threatening parasitic disease, transmitted by a sandfly. A survey was conducted to estimate the VL incidence in 45 villages located in the eastern part of Gedaref State, the main endemic focus of VL in Sudan. Between the 5^th of May and the 17^th of June 2011, we interviewed 17,702 households for a population of 94,369.

Sixteen individuals were diagnosed with primary VL through active case-detection, and 725 reported VL treatment over the past year. The overall incidence rate of VL over the past year was 7.0/1000 persons per year. The crude mortality rate over the mean recall period of 409 days was 0.13/10'000 persons per day. VL was a possible or probable cause for 19% of all deaths. Taking also into account the VL-specific mortality of 0.9/1000 per year, the incidence was estimated at 7.9/1000 per year. Overall, 12.5% of the population reported having been treated for VL in the past.

VL is a major public health issue in Gedaref. Active VL case detection had a very low yield in a context of adequate access to care. Such strategy seems redundant if patients already have access to care.

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Child
• Child, Preschool
• Cross-Sectional Studies
• Female
• Humans
• Incidence
• Infant
• Infant, Newborn
• Leishmaniasis, Visceral/epidemiology
• Male
• Middle Aged
• Rural Population
• Sudan/epidemiology
• Survival Analysis
• Young Adult

Visceral leishmaniasis (VL) caused by Leishmania donovani and Leishmania infantum/chagasi represents the second most challenging infectious disease worldwide, leading to nearly 500,000 new cases and 60,000 deaths annually. Zoonotic VL caused by L. infantum is a re-emergent canid zoonoses which represents a complex epidemiological cycle in the New world where domestic dogs serve as a reservoir host responsible for potentially fatal human infection and where dog culling is the only measure for reservoir control. Life-long immunity to VL has motivated development of prophylactic vaccines against the disease but very few have progressed beyond the experimental stage. No licensed vaccine is available till date against any form of leishmaniasis. High toxicity and increasing resistance to the current chemotherapeutic regimens have further complicated the situation in VL endemic regions of the world. Advances in vaccinology, including recombinant proteins, novel antigen-delivery systems/adjuvants, heterologous prime-boost regimens and strategies for intracellular antigen presentation, have contributed to recent advances in vaccine development against VL. Attempts to develop an effective vaccine for use in domestic dogs in areas of canine VL should be pursued for preventing human infection. Studies in animal models and human patients have revealed the pathogenic mechanisms of disease progression and features of protective immunity. This review will summarize the accumulated knowledge of pathogenesis, immune response, and prerequisites for protective immunity against human VL. Authors will discuss promising vaccine candidates, their developmental status and future prospects in a quest for rational vaccine development against the disease. In addition, several challenges such as safety issues, renewed and coordinated commitment to basic research, preclinical studies and trial design will be addressed to overcome the problems faced in developing prophylactic strategies for protection against this lethal infection.

• Leishmania donovani
• immunoprophylaxis
• kala-azar
• vaccines
• visceral leishmaniasis

• Animals
• Bayes Theorem
• Chromosome Mapping
• Disease Progression
• Dog Diseases/genetics
• Dog Diseases/physiopathology
• Dogs
• Genetic Markers/genetics
• Genetic Predisposition to Disease/genetics
• Genome-Wide Association Study
• Genotype
• Leishmaniasis/genetics
• Leishmaniasis/physiopathology
• Leishmaniasis/veterinary
• Likelihood Functions
• Mice
• Models, Statistical
• Phenotype
• Polymorphism, Single Nucleotide/genetics
• ROC Curve
• Sensitivity and Specificity

• G0600237 Medical Research Council
• G0100594 Medical Research Council
• BBS/E/D/05191132 Biotechnology and Biological Sciences Research Council
• G0901461 Medical Research Council
• G0900753 Medical Research Council

Leishmania species of the subgenus Leishmania and especially L. donovani are responsible for a large proportion of visceral leishmaniasis cases. The debate on the mode of reproduction and population structure of Leishmania parasites remains opened. It has been suggested that Leishmania parasites could alternate different modes of reproduction, more particularly clonality and frequent recombinations either between related individuals (endogamy) or between unrelated individuals (outcrossing) within strongly isolated subpopulations. To determine whether this assumption is generalized to other species, a population genetics analysis within Leishmania donovani complex strains was conducted within a single village. The results suggest that a mixed-mating reproduction system exists, an important heterogeneity of subsamples and the coexistence of several genetic entities in Sudanese L. donovani. Indeed, results showed significant genetic differentiation between the three taxa (L. donovani, L. infantum and L. archibaldi) and between the human or canine strains of such taxa, suggesting that there may be different imbricated transmission cycles involving either dogs or humans. Results also are in agreement with an almost strict specificity of L. donovani stricto sensu to human hosts. This empirical study demonstrates the complexity of population structure in the genus Leishmania and the need to pursue such kind of analyses at the smallest possible spatio-temporal and ecological scales.

Leishmaniases are a serious public health problem, especially in developing countries, caused by Leishmania parasites and transmitted by sandfly bites. More information is needed on the population biology of these pathogens for diagnostic and epidemiological inquiries and for drug and vaccine elaboration. For studies dealing with the population genetics, exploring the genetic patterns of such organisms at microgeographic scales is fundamental. In this context, we made a population genetic study, based on 20 microsatellite loci, on 61 strains of Leishmania donovani complex collected in a Sudanese village, Babar El Fugara, during the epidemic of 1996–2000. Results showed that considering the whole sample as a single population was not adequate because of the coexistence of several genetic entities and a genetic differentiation between the human or canine strains. In addition, our findings suggested that clonality may have a strong impact on the L. donovani complex, unlike other Leishmania species. This study demonstrates the need to pursue population genetics studies in Leishmania species from sampling designs that control maximum possible confounding factors and to elaborate such kinds of analyses at the smallest possible spatio-temporal and ecological scales.

• Animals
• Asia, Southeastern/epidemiology
• Cattle/parasitology
• Disease Vectors
• Humans
• Insect Control/methods
• Leishmaniasis, Visceral/epidemiology
• Leishmaniasis, Visceral/prevention & control
• Psychodidae
• Risk Factors
• Rural Population

• Animals
• Humans
• Interleukin-17/physiology
• Interleukin-1beta/biosynthesis
• Interleukin-23/biosynthesis
• Interleukin-6/biosynthesis
• Interleukins/physiology
• Leishmaniasis, Visceral/immunology
• Leukocytes, Mononuclear/immunology
• Th1 Cells/immunology
• Th2 Cells/immunology
• Interleukin-22

• Animals
• Communicable Disease Control
• Global Health
• Humans
• Leishmania/physiology
• Leishmaniasis/epidemiology
• Leishmaniasis/parasitology
• Leishmaniasis/prevention & control