Zoonotic Visceral Leishmaniasis Research Articles

A Canine-Directed Chimeric Multi-Epitope Vaccine Induced Protective Immune Responses in BALB/c Mice Infected with Leishmania infantum.

Leishmaniases are complex vector-borne diseases caused by intracellular parasites of the genus Leishmania. The visceral form of the disease affects both humans and canids in tropical, subtropical, and Mediterranean regions. One health approach has suggested that controlling zoonotic visceral leishmaniasis (ZVL) could have an impact on the reduction of the human incidence of visceral leishmaniasis (VL). Despite the fact that a preventive vaccination could help with leishmaniasis elimination, effective vaccines that are able to elicit protective immune responses are currently lacking. In the present study, we designed a chimeric multi-epitope protein composed of multiple CD8+ and CD4+ T cell epitopes which were obtained from six highly immunogenic proteins previously identified by an immunoproteomics approach, and the N-termini of the heparin-binding hemagglutinin (HBHA) of Mycobacterium tuberculosis served as an adjuvant. A preclinical evaluation of the candidate vaccine in BALB/c mice showed that when it was given along with the adjuvant Addavax it was able to induce strong immune responses. Cellular responses were dominated by the presence of central and effector multifunctional CD4+ and CD8+ T memory cells. Importantly, the vaccination reduced the parasite burden in both short-term and long-term vaccinated mice challenged with Leishmania infantum. Protection was characterized by the continuing presence of IFN-γ+TNFα+-producing CD8+ and CD4+ T cells and increased NO levels. The depletion of CD8+ T cells in short-term vaccinated mice conferred a significant loss of protection in both target organs of the parasite, indicating a significant involvement of this population in the protection against L. infantum challenge. Thus, the overall data could be considered to be a proof-of-concept that the design of efficacious T cell vaccines with the help of reverse vaccinology approaches is possible.

Potential distributions of phlebotomine sandfly vectors of human visceral leishmaniasis caused by Leishmania infantum in Morocco.

Zoonotic visceral leishmaniasis is a common vector-borne systemic disease caused by Leishmania infantum (Kinetoplastida: Trypanosomatidae). In Morocco the situation is complex: many sandfly species have been collected in areas in which the disease is endemic, but only Phlebotomus ariasi, Phlebotomus perniciosus and Phlebotomus longicuspis (Diptera: Psychodidae) have been confirmed to have vectorial roles. The objective of the present study was to ascertain the potential distribution of L. infantum and its vectors in Morocco, using ecological niche modelling. Vector records were obtained from field collections of the Laboratory team and from previously published entomological observations. Epidemiological data for L. infantum modelling were obtained from Moroccan Ministry of Health reports. The jackknife test indicated that the bioclimatic variables with the greatest influence on model development for all species were annual precipitation and precipitation in the driest quarter of the year. MaxEnt model representations for sandfly species that act as vectors of L. infantum showed the widespread geographic distribution of these species in Morocco, specifically in northern and central Morocco, where foci of visceral leishmaniasis are found. The ecological niche modelling points out areas in which the probability of occurrence of these species is higher. This information should be considered as a starting point for further research to fully elucidate the ecology and epidemiology of these species, as well as of the pathogens they transmit.

A new zoonotic visceral leishmaniasis dynamic transmission model with age-structure

Abstract Visceral leishmaniasis (VL) is a fatal, neglected tropical disease primarily caused by Leishmania donovani (L. donovani) and Leishmania infantum (L. infantum). According to VL infectious data reports from severely affected countries, children and teenagers (ages 0–20) have a significantly higher vulnerability to VL infection than other populations. This paper utilizes an infected function (by age) established from epidemic prevalence data to propose a new partial differential equation (PDE) model for infection transmission patterns for various age groups. This new PDE model can be used to study VL epidemics in time and age dimensions. Disease-free and endemic equilibriums are discussed in relation to theoretical stability of the PDE system. This paper also proposes system output adjustment using historical VL data from the World Health Organization. Statistical methods such as the moving average and the autoregressive methods are used to calibrate estimated prevalence trends, potentially minimizing differences between stochastic stimulation results and reported real-world data. Results from simulation experiments using the PDE model were used to predict the worldwide VL severity of the epidemic in the next four years (from 2017 to 2020).

Co-circulation of Toscana virus and Leishmania infantum in a focus of zoonotic visceral leishmaniasis from Central Tunisia

In the Mediterranean basin, sand flies are vectors of Leishmania parasites and phleboviruses affecting humans and animals. In this study, we aimed to investigate phlebovirus and Leishmania parasites circulating in a focus of zoonotic visceral leishmaniasis (ZVL) located in a highly irrigated area within the arid Central Tunisia, known mainly to be endemic for zoonotic cutaenous leishmaniasis (ZCL) caused Leishmania major and transmitted by Phlebotomus papatasi. Sand flies were collected using CDC light traps in the village of Saddaguia, an emergent focus of ZVL located in Central Tunisia during September-October 2014, 2015, and 2016. Pools of live female sand flies were screened for phleboviruses and Leishmania by nested PCR in the polymerase gene and kinetoplast minicircle DNA, respectively. Dead sand flies were identified morphologically to species level. Sand flies of the subgenus Larroussius mainly Phlebotomus perfiliewi, Phlebotomus perniciosus, and Phlebotomus longicuspis were predominant in this ZVL focus compared to P. papatasi. A total of 1932, 1740, and 444 sand flies were tested in 2014, 2015 and 2016, respectively. Pathogen screening performed on 4116 sand flies distributed in 148 pools revealed the presence of Leishmania infantum and Toscana virus. The minimum infection rates of sand flies with TOSV in 2014, 2015, and 2016 were 0.05%, 011%, and 0.22%, respectively. The minimum infection rates of sand flies with L. infantum in 2014, 2015, and 2016 were 0.25%, 012%, and 0.79%, respectively. No L. major was detected during the 3-years investigation in this ZVL focus. Our results showed clearly the endemic co-circulation of TOSV and L. infantum in this emergent ZVL focus. However, no co-infection of TOSV and L. infantum was detected in any of the sand fly pools investigated during the three years period. TOSV was isolated from positive pools in 2015. Phylogenetic analysis showed that the Tunisian strains of TOSV belonged to the sublineage A. Based on the present findings, our results provided strong evidence that TOSV and L. infantum are transmitted by the same predominant sand fly species of the subgenus Larroussius, and subsequently, humans and dogs could be co-infected through co-infected or successive infected bites. Our results showed clearly that the development of irrigation in arid areas contributed significantly to the establishment of stable transmission cycles of L. infantum and TOSV and subsequently to the emergence of a ZVL focus within this arid bio-geographical area characterized by the presence of multiple foci of ZCL located outside the study site. Thus, more studies are needed to better understand the impact of RNA viruses shared by vectors and reservoir hosts of L. infantum on the development of zoonotic visceral leishmaniasis.

Visceral Leishmaniasis - China, 2015-2019.

What is already known about this topic?Visceral leishmaniasis (VL) is an important vector-borne disease in rural areas of western China. The spreading of VL made its prevention and control become more complicated.What is added by this report?The number of VL cases decreased from 2015 (n=498) to 2019 (n=166). However, the mountain-type zoonotic visceral leishmaniasis (MT-ZVL) cases increased from 2015 (n=82, 16.5%) to 2019 (n=122, 73.5%). In addition, both number and proportion of imported cases increased from 2015 (n=18, 3.6%) to 2019 (n=41, 24.7%). The re-emergence of MT-ZVL was considerable; 13 historically-endemic counties reported 48 indigenous cases. Infants and young children were the high risk population of VL (848, 62.4%) followed by farmers (303, 22.3%).What are the implications for public health practice?Both MT-ZVL and imported cases showed an increasing trend in China. Therefore, two actions are needed to control VL: 1) to prevent re-emergence and spreading of MT-ZVL; and 2) to ensure timely diagnosis and appropriate treatment to avoid fatal VL cases, especially in non-endemic areas.

Distribution of Suitable Environments for Phlebotomus chinensis as the Vector for Mountain-Type Zoonotic Visceral Leishmaniasis - Six Provinces, China.

What is already known on this topic? Phlebotomus chinensis(P. chinensis) is a sandfly and the main vector of mountain-type zoonotic visceral leishmaniasis (MT-ZVL) in China. However, the distribution of suitable environments for the vector has not been studied yet. What is added by this report? This study found that temperate hilly zones in midwestern China are suitable for P. chinensis survival with appropriate environmental factors such as moderate normalized difference vegetation value (NDVI), land use type, landform, temperature, and vegetation. Suitable living conditions for the high-density P. chinensis that caused the reemergence of MT-ZVL already existed. What are the implications for public health practice? Targeted strategies should be implemented to control the vector and the reemergence of MT-ZVL, such as by strengthening key environment monitoring and taking accurate measures for residents, mobile and migrant populations.

Are backyard characteristics relevant factors for the occurrence of human visceral leishmaniasis in Central-Western Brazil?

This retrospective case-control study aimed to investigate the factors associated with the occurrence of human visceral leishmaniasis (VL) in the municipality of Rondonópolis, which is a highly endemic area for VL in Central-Western Brazil. All VL cases reported in Rondonópolis from 2011 to 2016 were included. For each case, two neighborhood- and age-matched controls with the absence of past and present history of VL and negative rk39-based immunochromatographic test, were recruited. Data were retrospectively collected through interviews that assessed socioeconomic aspects, housing features, backyard characteristics, presence of animals and daily habits. A multivariate conditional logistic regression analysis was used to identify factors associated with human VL. During the study period, 81 VL cases were reported in Rondonópolis, of which 37 (45.7%) were included in this study. Seventy controls were also included. The variables associated with VL occurrence were the outdoor location of a bathroom and/or kitchen separated from the rest of the house (OR 7.8; 95% CI 2.1 to 29.5), the presence of a vegetable garden (OR 5.3; 95% CI 1.3 to 21.2) and the presence of decaying fruits (OR 10.7; 95% CI 2.0 to 52.1) in the backyard. Our findings suggest an association between backyard characteristics and VL. This may be useful in guiding preventive and control measures against zoonotic VL worldwide.

Bayesian compartmental models and associated reproductive numbers for an infection with multiple transmission modes.

Zoonotic visceral leishmaniasis (ZVL) is a serious neglected tropical disease that is endemic in 98 countries. ZVL is primarily transmitted via a sand fly vector. In the United States, it is enzootic in some canine populations; it is transmitted from infectious mother to pup transplacentally, and vector-borne transmission is absent. This absence affords a unique opportunity to study (1) vertical transmission dynamics in dogs and (2) the importance of vertical transmission in maintaining an infectious reservoir in the presence of a vector. In this paper, we present Bayesian compartmental models and reproductive number formulations to examine (1) and (2), providing a mechanism to plan and evaluate interventions in regions where both transmission modes are present. First, we propose an individual-level susceptible, infectious, removed (SIR) model to study the effect of maternal infection status during pregnancy on pup infection progression. We provide evidence that pups born to diagnostically positive mothers during pregnancy are more likely to become diagnostically positive both earlier in life, and at some point during their lifetime, than those born to diagnostically negative mothers. Second, we propose a population-level SIR model to study the impact of a vertically maintained reservoir on propagating infection in a naive canine population through emergent vector transmission using simulation studies. We also present reproductive numbers to quantify contributions of vertically infected and vector-infected dogs to maintaining infection in the population. We show that a vertically maintained canine reservoir can propagate infection in a theoretical naive population in the presence of avector.

Geo-climatic factors in a newly emerging focus of zoonotic visceral leishmaniasis in rural areas of north-eastern Iran.

Visceral leishmaniasis (VL) is the fatal form of leishmaniasis. A newly emerging focus of zoonotic VL (ZVL) including 13 villages has been reported from Maraveh Tappeh County, Golestan province, north-eastern Iran. We investigated the effect of climatic and environmental factors on the occurrence of disease in this focus by geographical information systems (GIS) approaches and logistic regression models. The incidence rate of ZVL in human and dog population was estimated 1.2% and 27.3%, respectively, in the studied areas. Rock soil type (OR=11.7), rainfall (OR=1.04) and elevation (OR=0.99) were found as determinants of ZVL. Also, almost all infected villages were in close proximity of rivers. Cavities of rock soil around rivers are assumed as suitable areas for sandfly resting and growth by providing shadow and moisture. Rainfall also provides appropriate moisture in semi-arid regions for survival of sandflies. The negative effect of higher altitude can be explained by some sandfly life-limiting conditions like freezing weather. Accordingly, regions with lower altitude and higher rainfall, covered by rock and in close proximity of rivers, are the hazard zones for ZVL in the Maraveh Tappeh. Air humidity, temperature, land cover type and slope were not predictors of disease in the current study. Further investigations on human population movement, probable reservoirs and vectors of disease can provide valuable data for modelling the future distribution of ZVL in the Iranian province.

Early antibody response and clinical outcome in experimental canine leishmaniasis

Infected dogs are the main reservoir of zoonotic visceral leishmaniasis, a widespread parasitic disease caused by Leishmania infantum. Therefore, the control of canine infections is required to reduce the incidence of human cases. Disease outcome in dogs depends on the fine balance between parasite virulence and efficacy of the immune system. Thus, knowledge of early response could yield relevant information for diagnosis and follow-up. In our study, 20 Beagle dogs were intravenously infected with 108 amastigotes of a fresh isolate of L. infantum and monitored along 16 weeks post inoculation. Specific antibody response and clinical evolution of infected animals were highly variable. Immunofluorescence antibody test (IFAT) and enzyme linked immunosorbent assay (ELISA) were useful to assess infection status, although only ELISA with promastigote-coated plates and, particularly, western blotting (WB) allowed an early diagnosis. Prominent antigens were identified by mass peptide fingerprinting. Chaperonin HSP60, 32 and 30 KDa antigens were recognized by all dogs on week 10 post infection. This suggests that these antigens may be valuable for early diagnosis. Advanced infection showed, in addition, reactivity to HSP83 and HSP70. Disease outcome did not show a clear relationship with ELISA or IFAT titers. Correlation between the clinical status and the combined reactivity to some antigens sustains their use for diagnosis and follow-up.

Peptide-based vaccine successfully induces protective immunity against canine visceral leishmaniasis

Dogs are the main reservoir of zoonotic visceral leishmaniasis. Vaccination is a promising approach to help control leishmaniasis and to interrupt transmission of the Leishmania parasite. The promastigote surface antigen (PSA) is a highly immunogenic component of Leishmania excretory/secretory products. A vaccine based on three peptides derived from the carboxy-terminal part of Leishmania amazonensis PSA and conserved among Leishmania species, formulated with QA-21 as adjuvant, was tested on naive Beagle dogs in a preclinical trial. Four months after the full course of vaccination, dogs were experimentally infected with Leishmania infantum promastigotes. Immunization of dogs with peptide-based vaccine conferred immunity against experimental infection with L. infantum. Evidence for macrophage nitric oxide production and anti-leishmanial activity associated with IFN-γ production by lymphocytes was only found in the vaccinated group. An increase in specific IgG2 antibodies was also measured in vaccinated dogs from 2 months after immunization. Additionally, after challenge with L. infantum, the parasite burden was significantly lower in vaccinated dogs than in the control group. These data strongly suggest that this peptide-based vaccine candidate generated cross-protection against zoonotic leishmaniasis by inducing a Th1-type immune response associated with production of specific IgG2 antibodies. This preclinical trial including a peptide-based vaccine against leishmaniasis clearly demonstrates effective protection in a natural host. This approach deserves further investigation to enhance the immunogenicity of the peptides and to consider the possible engineering of a vaccine targeting several Leishmania species.

A single oral dose of fluralaner (Bravecto®) in dogs rapidly kills 100% of blood-fed Phlebotomus perniciosus, a main visceral leishmaniasis vector, for at least 1 month after treatment.

Dogs are the reservoir host of zoonotic visceral leishmaniasis (VL) caused by Leishmania infantum (Kinetoplastida: Trypanosomatidae). Both subclinically‐infected and sick animals can be infectious to competent phlebotomine vectors. The degree and duration of insecticidal efficacy of an oral dose of fluralaner (Bravecto®; Merck Animal Health) was determined in dogs exposed to bites of Phlebotomus perniciosus (Diptera: Psychodidae), a main Mediterranean vector of VL. Twelve dogs allocated to two groups of six animals each were included in a parallel‐group designed, negative‐controlled, randomized, blinded, single‐centre efficacy study. Group 2 was treated with fluralaner on day 0, and sand‐fly exposure of both groups was performed on days 1, 28 and 84. Viability of blood‐fed females was assessed up to 96 h after exposure and efficacy was measured as the survival rate of specimens fed on Group 2 versus those fed on Group 1. A mortality of 100% was recorded at 24 h in females fed on Group 2 at both days 1 and 28. Significant insecticidal efficacy was still observed on day 84, with > 50% mortality recorded by 48 h post blood meal in Group 2. Fluralaner treatment of dogs represents a promising and affordable method for reducing the pool of infected vectors in endemic settings of zoonotic VL.

The Use of Specific Serological Biomarkers to Detect CaniLeish Vaccination in Dogs.

Canine leishmaniosis (CanL) prevention in the Mediterranean basin is considered essential to stop human zoonotic visceral leishmaniasis. In this context, vaccination of dogs is expected to have a significant impact in disease control. CaniLeish® (Virbac Animal Health) is one of a few CanL vaccines that are at this moment licensed in Europe. This vaccine contains purified excreted-secreted proteins of Leishmania having several antigens/immunogens with potential to influence serological response. Therefore, it is important to know if CaniLeish vaccination increased the diagnostic challenges associated with conventional serology, limiting the value of some antigens. To address this 20 dogs from a cohort of 35 healthy dogs that were vaccinated, maintained indoor for 1 month and then returned to their natural domiciles for 2 years. After this period, they were re-called to evaluate their clinical/parasitological condition and assess the evolution of seroreactivity against different antigens: soluble promastigote Leishmania antigens (SPLA), recombinant protein Leishmania infantum cytosolic peroxiredoxin, recombinant protein K39 (rK39), recombinant protein K28 and recombinant kinesin degenerated derived repeat using ELISA. Two years after vaccination all vaccinated non-infected animals were seropositive for SPLA. For the other antigens the serological profile was indistinguishable from non-infected animals. Moreover, vaccinated animals presented a characteristic relative serological profile, with higher normalized serological response to SPLA than rK39. This fact enabled to distinguish with sensitivity 92.3% and specificity 95.4%, vaccinated non-infected dogs from infected and non-infected dogs. Ultimately, relative serological profile enabled the detection of healthy vaccinated animals enabling more accurate serological surveys.

Fractional investigations of zoonotic visceral leishmaniasis disease with singular and non-singular kernel

Memory has a great impact to study the dynamics of any real epidemic process in a better way. An epidemic model including memory effect is governed by fractional differential equations. In the present paper we explore the dynamics of the zoonotic visceral leishmaniasis (ZVL) disease using fractional derivative in both the Caputo and Atangana-Baleanu sense. The proposed model in the Caputo sense is solved by the well-known method known as modified differential transform method (MDTM), which is efficient and reliable. Further, the solution for the model with Atangana-Baleanu derivative is obtained by the modified Adams-Bashforh method. Numerical simulations are presented by using a different value of the fractional order parameter $ \alpha$ . The numerical results obtained through the MDTM and the modified Adams-Bashforh method are reasonable and provide useful information in the non-integer case. Numerical results presented for the fractional order parameter $ \alpha$ and in the integer case for the Caputo derivative model are compared with the Runge-Kutta method which gives good agreement. The application of Atangana-Baleanu derivative, the Caputo derivative and the use of the numerical approaches, MDTM, Adams Bashforth and the Runge-Kutta method (for the integer case) for an epidemic model is a novel practice and provides more flexible and deeper information about the complexity of the dynamics of ZVL.

A nationwide survey of Leishmania infantum infection in cats and associated risk factors in Italy.

Though scantly investigated, Leishmania infantum infection and clinical cases of leishmaniasis in cats have been recently reported in several countries of the Mediterranean basin, with large variability in prevalence data. A major limitation in the comparability of the data available is attributed to the differences in diagnostic techniques employed and cat populations sampled. The aim of this study was to assess the prevalence of L. infantum infection in owned cats across Italy by serological and molecular tests and the identification of potential risk factors. Blood samples from 2,659 cats from northern (n = 1,543), central (n = 471) and southern (n = 645) Italy were tested for antibodies against L. infantum, by an immunofluorescence antibody test and for the parasites’ DNA, by real-time PCR. Samples were additionally screened for feline leukemia virus (FeLV) and feline immunodeficiency virus (FIV) proviral DNAs. An overall cumulative L. infantum prevalence of 3.9% was recorded by serology (3.3%) and/or qPCR (0.8%), with a higher rate (10.5%) in southern Italy. The risk of L. infantum infection in cats was significantly associated to the geographical areas (South vs North and Centre; p<0.0001), age class (from 19 months to 6 years old vs ≤18 months old, p = 0.0003), neutering status (not neutered vs neutered, p = 0.0028) and FIV infection (p = 0.0051).Though the role of cats in the epidemiology of L. infantum is still debated, our findings indicate that cats are exposed to and/or infected by this protozoan, mainly in endemic regions of Italy. Hence, a standardization of procedures for a prompt diagnosis of L. infantum infection in cats and for screening cat population is crucial for a better understanding of the epidemiology of feline leishmaniasis, and of the potential role of cats in the transmission cycle of zoonotic visceral leishmaniasis.

Factors associated with Leishmania spp. infection in domestic dogs from an emerging area of high endemicity for visceral leishmaniasis in Central-Western Brazil

The factors associated with Leishmania spp. infection in dogs are still poorly understood. This study aimed to identify such factors among domestic dogs from the Brazilian municipality of Rondonópolis, which recently emerged as an endemic area with intense transmission of human visceral leishmaniasis (VL). It was a household-based cross-sectional study conducted between 2016 and 2017. Interviews were conducted with 405 dog owners considering their socioeconomic characteristics, and environmental aspects of the household and its adjacent areas. In addition, 600 dogs were evaluated regarding physical characteristics, behavior, and care provided by the owner. Seropositive animals were those that showed reactivity in a rapid immunochromatographic test and enzyme-linked immunosorbent assay, which are currently recommended for canine visceral leishmaniasis (CVL) diagnosis in Brazil. A multivariable logistic regression analysis was employed to determine the associated factors. Low social class [OR = 2.0; 95%CI = (1.2–3.2)], presence of acerola tree (Malpighia emarginata) in the yard [OR = 2.2; 95%CI = (1.2–4.1)], presence of more than one dog in the household [OR = 2.0; 95%CI = (1.3–3.3)], horse and/or cattle breeding [OR = 12.0; 95%CI = (1.9–73.6)], existence of houses with yard adjacent to the home [OR = 4.0; 95%CI = (1.3–12.2)], presence of apparent signs consistent with CVL [OR = 10.6; 95%CI = (5.8–19.4)], dog staying mostly in the yard during the day [(OR = 4.8; 95%CI = (1.1–21.4)], and lack of cleaning of the dog's shelter [(OR = 1.9; 95%CI = (1.1–3.2)] were identified as the factors associated with Leishmania spp. infection. These results support the importance of socioeconomic and environmental aspects in the occurrence of Leishmania spp. infection. In addition, they may be useful in guiding control strategies in areas where zoonotic VL is endemic.

Updates on the distribution and diversity of sand flies (Diptera: Psychodidae) in Romania

BackgroundPhlebotomine sand flies (Diptera: Psychodidae) are haematophagous insects that transmit the protozoan parasite Leishmania infantum (Kinetoplastida: Trypanosomatidae), the main causative agent of both zoonotic visceral leishmaniasis (VL) and canine leishmaniasis (CanL) in the Mediterranean basin. Eight species of sand flies have been previously recorded in Romania: Phlebotomus papatasi, Phlebotomus alexandri, Phlebotomus sergenti, Phlebotomus perfiliewi, Phlebotomus neglectus, Phlebotomus longiductus, Phlebotomus balcanicus and Sergentomyia minuta. Three of them (P. perfiliewi, P. neglectus and P. balcanicus) were incriminated as vectors of L. infantum. Recent reports of autochthonous CanL in Romania require updates on sand fly distribution and diversity in this country.MethodsBetween 2013–2014 and 2016–2018, CDC light traps and mouth aspirators were used to collect sand flies in 132 locations from Romania, indoors and around various animal species shelters. Species identification of collected specimens was done using morphological keys, genetic tools and MALDI-TOF protein profiling.ResultsSand flies were present in seven localities (5.3%): Eibenthal, Baia Nouă, Gura Văii (south-western Romania, Mehedinţi County); Fundătura, Pâhneşti, Epureni (eastern Romania, Vaslui County); and Schitu (southern Romania, Giurgiu County). Of the total number of collected sand flies (n = 251), 209 (83.27%) were Phlebotomus neglectus, 39 (15.53%) P. perfiliewi, 1 (0.40%) P. papatasi, 1 (0.40%) P. balcanicus and 1 (0.40%) P. sergenti (sensu lato).ConclusionsWe confirmed the presence of five sand fly species previously recorded in Romania. However, their updated distribution differs from historical data. The diversity of sand fly species in Romania and their presence in areas with Mediterranean climatic influences constitutes a threat for the reemergence of vector-borne diseases. In the context of CanL and VL reemergence in Romania, but also due to imported cases of the diseases in both humans and dogs, updates on vector distribution are imperative.

An Epidemic Model of Zoonotic Visceral Leishmaniasis with Time Delay

This paper presents a mathematical model with time delay for the transmission dynamics of zoonotic visceral leishmaniasis (ZVL which is caused by protozoan parasite leishmania infantum and transmitted by female sandflies). Qualitative analysis of the ODE version of the model reveals that the disease-free equilibrium of the model is globally asymptotically stable when the basic reproduction number, R0, is less than unity. Using time delay as a bifurcation parameter in the delay-differential version of the model, it has been shown that the incubation period has a significant effect on the stability of the equilibria and we derived the condition for Hopf bifurcation to occur.

Spatio-temporal modelling of Leishmania infantum infection among domestic dogs: a simulation study and sensitivity analysis applied to rural Brazil

BackgroundThe parasite Leishmania infantum causes zoonotic visceral leishmaniasis (VL), a potentially fatal vector-borne disease of canids and humans. Zoonotic VL poses a significant risk to public health, with regions of Latin America being particularly afflicted by the disease. Leishmania infantum parasites are transmitted between hosts during blood-feeding by infected female phlebotomine sand flies. With a principal reservoir host of L. infantum being domestic dogs, limiting prevalence in this reservoir may result in a reduced risk of infection for the human population. To this end, a primary focus of research efforts has been to understand disease transmission dynamics among dogs. One way this can be achieved is through the use of mathematical models.MethodsWe have developed a stochastic, spatial, individual-based mechanistic model of L. infantum transmission in domestic dogs. The model framework was applied to a rural Brazilian village setting with parameter values informed by fieldwork and laboratory data. To ensure household and sand fly populations were realistic, we statistically fitted distributions for these entities to existing survey data. To identify the model parameters of highest importance, we performed a stochastic parameter sensitivity analysis of the prevalence of infection among dogs to the model parameters.ResultsWe computed parametric distributions for the number of humans and animals per household and a non-parametric temporal profile for sand fly abundance. The stochastic parameter sensitivity analysis determined prevalence of L. infantum infection in dogs to be most strongly affected by the sand fly associated parameters and the proportion of immigrant dogs already infected with L. infantum parasites.ConclusionsEstablishing the model parameters with the highest sensitivity of average L. infantum infection prevalence in dogs to their variation helps motivate future data collection efforts focusing on these elements. Moreover, the proposed mechanistic modelling framework provides a foundation that can be expanded to explore spatial patterns of zoonotic VL in humans and to assess spatially targeted interventions.

Review of Leishmaniasis in the Middle East and North Africa.

Cutaneous and visceral forms of leishmaniasis are the most important protozoan infection in the Middle East and North Africa (MENA). Review the current knowledge on leishmaniasis in the MENA. The data presented in this review are gathered primarily from WHO reports and from an extensive literature search on PubMed. There are four cycles of transmission of leishmaniasis: zoonotic cutaneous leishmaniasis (ZCL), induce by Leishmania (L.) major, transmitted by Phlebotomus (P.) papatasi, with rodent species of Psammomys obesus, Meriones libycus, Nesokia indica, and Rhombomys opimus are considered as host reservoirs. Zoonotic visceral leishmaniasis (ZVL) is inducing by L. infantum, transmitted by several Phlebotomus spp. of the sub-genus Larroussius and mainly P. perniciosus in more than one-half of the MENA countries and the dog species of Canis familiaris are considered as the main reservoirs. Anthroponotic cutaneous leishmaniasis (ACL), induce by L. tropica and transmitted by P. sergenti, without any non-human reservoir in most cases. Anthroponotic visceral leishmaniasis (AVL) induces by L. donovani spreads through P. alexandri, circulates exclusively in humans. There are many challenges facing the successful control of leishmaniasis. However, there is continuing research into the treatment of leishmaniasis and potentially vaccinations for the disease.