Control Tools

• Diagnostics availability

• Commercial diagnostic kits available worldwide

  Commercial serological diagnostic kits are available, whereas culture-based diagnostics and field-level molecular tests (e.g., PCR) are not commercially accessible and remain confined to research settings.

  Further info: List of animal health diagnostics

  GAPS

  There is a general need for more sensitive diagnostics to detect asymptomatic carriers—especially in dogs—and to differentiate between infectious and non-infectious stages. Portable isothermal PCR platforms have recently emerged, but still require proper validation and market access.

  The full gap analysis matrices for Leishmaniasis can be founf on the website and downloaded here.

• Diagnostic kits validated by International, European or National Standards

  Some serological kits, such as the rK39 dipsticks, have been validated by the WHO and national control programs in countries like India and Sudan

  GAPS

  Molecular methods lack harmonized validation across endemic regions.

• Diagnostic method(s) described by International, European or National standards

  Diagnostic methods for leishmaniasis are extensively described in international guidelines. The WOAH Terrestrial Manual details diagnostic approaches for animal leishmaniasis, while the WHO provides standard protocols for human visceral leishmaniasis (VL), including serological and parasitological methods.

  GAPS

  Practical implementation, diagnostic capacities, and interpretation of these guidelines vary widely across regions due to differences in resources, infrastructure, and disease focus.

• Commercial potential for diagnostic kits worldwide

  The commercial potential for diagnostic kits is emerging, especially in endemic regions where demand for rapid, point-of-care diagnostics is growing. While human diagnostics have made progress, veterinary applications—particularly for canine leishmaniasis—represent an unmet and underserved market, notably in Latin America and parts of Southern Europe

  GAPS

  However, barriers such as lack of DIVA-compatible tests, limited regulatory harmonization, and cost constraints continue to hinder broader adoption.

• DIVA tests required and/or available

  DIVA tests based on recombinant antigens have been developed for human leishmaniasis in clinical contexts. In the veterinary field, no commercial DIVA test is currently available.

  GAPS

  There is a clear lack of validated and commercially available DIVA tests for canine leishmaniasis. This limits the ability to distinguish vaccinated from infected dogs, which is critical for monitoring vaccination campaigns and ensuring effective surveillance. In addition, no harmonized DIVA-compatible diagnostic/vaccine system exists. Barriers such as lack of DIVA-compatible tests, limited regulatory harmonization, and cost constraints continue to hinder broader adoption of integrated control strategies.

• Vaccines availability

• Commercial vaccines availability (globally)

  Several commercial vaccines are available for canine leishmaniasis: Leish-Tec® in Brazil (rA2 protein + QA-21 saponin, under conditional license), and LetiFend® (recombinant Protein Q) in the EU. These vaccines reduce the risk of clinical disease but do not confer sterilizing immunity. No human vaccine is currently licensed.

  GAPS

  No vaccine currently prevents infection or transmission. Vaccines are unaffordable in many endemic settings. There is no licensed human vaccine. Lack of sterilizing immunity and limited data on long-term protection limit impact on disease transmission.

• Marker vaccines available worldwide

  None.

  GAPS

  There is a need for DIVA-compatible vaccines and validated companion diagnostics, especially for use in surveillance and disease control programs. This is particularly relevant in countries with test-and-cull policies or widespread vaccination.

• Marker vaccines authorised in Europe

  1. recombinant Protein Q from L. infantum MON-1.

  2. purified excreted-secreted proteins of L. infantum and with QA-21 saponin as adjuvant.

• Effectiveness of vaccines / Main shortcomings of current vaccines

  Available canine vaccines reduce the risk of disease progression and clinical signs. LetiFend® reduces the likelihood of disease fivefold. No sterilizing immunity is achieved, and vaccinated dogs may remain infectious. No validated immune correlates of protection have been established.

  GAPS

  No vaccine prevents infection or guarantees absence of transmission. There is a lack of standard challenge models (especially with natural sand fly exposure), validated immune biomarkers, and long-term efficacy data. Safety profiles require further clarification.

• Commercial potential for vaccines

  There is significant market potential in Western Europe and urban areas of Latin America. Interest is growing in endemic regions, particularly where canine leishmaniasis is prevalent.

  GAP Affordability of a canine vaccine may be an issue in the Mediterranean basin outside Western EU.

• Regulatory and/or policy challenges to approval

  Both vaccines comply with EMEA regulations. Provided a vaccine candidate meets all expected specifications (including manufacturing under GMP conditions) no specific unmanageable regulatory challenge is expected.

  GAPS

  Regulatory hurdles increase with live attenuated or vectored platforms. Outside the EU, lack of harmonized veterinary vaccine regulations complicates registration. Absence of DIVA-compatible strategies may affect approval or field deployment in countries with test-and-cull or export control measures.

• Commercial feasibility (e.g manufacturing)

  Commercial feasibility is strongly influenced by the vaccine platform. Protein-based and recombinant subunit vaccines have moderate production costs and are scalable under GMP conditions. Most current efforts are focused on recombinant protein vaccines due to their favorable safety profile and manufacturability.

  GAPS

  Live-attenuated and viral-vectored vaccines face complex regulatory and biosafety challenges that impact scalability. Cold chain requirements and adjuvant availability may limit deployment in resource-poor settings. There is limited comparative analysis of production cost, yield, and industrial viability across platforms. Lack of standardized processes and insufficient industrial partnerships also constrain feasibility.

• Opportunity for barrier protection

  Barrier protection strategies (e.g., insecticide collars, topical repellents) can offer individual protection for dogs. However, geographic containment is increasingly unreliable due to dog movement and the spread of competent vectors into non-endemic areas. Border controls and pet movement restrictions are in place in some regions, but inconsistently enforced.

  GAPS

  There is limited research on the population-level effectiveness of barrier methods in preventing transmission. Vector expansion due to climate change reduces the effectiveness of geographic barriers. Lack of long-acting and affordable repellents, and the absence of harmonized movement regulations, hinder consistent barrier protection implementation.

• Pharmaceutical availability

• Current therapy (curative and preventive)

  In the EU, only injectable meglumine antimoniate and oral miltefosine are licensed for use in dogs. Other compounds (e.g., allopurinol, amphotericin B) are used off-label. These therapies achieve clinical improvement but not radical parasitological cure. In humans, various treatment options are available, but dogs generally do not respond as effectively.

  GAPS

  No therapy provides a radical cure or effective prophylaxis in dogs. Protocol diversity causes inconsistent practices and confusion. Long-term parasite persistence and relapse are common. The use of human drugs in dogs raises the risk of resistance development. Data on the optimal therapeutic combination and long-term outcomes in dogs are limited.

• Future therapy

  New candidates in early research and pre-clinical phases.

  GAPS

  There is a lack of validated novel drug targets for canine leishmaniasis. Few candidates have reached advanced development stages. No effective therapeutic combinations have been standardized. Safety, cost, and ease of administration remain unresolved challenges for future veterinary drugs

• Commercial potential for pharmaceuticals

  Commercial demand for canine leishmaniasis pharmaceuticals is high in Western Europe, driven by veterinary care practices and pet ownership. In other regions, affordability and access are limiting factors.

  GAPS

  The existing use of off-label products reduces incentive for pharmaceutical investment. The cost of regulatory approval and limited market size restrict commercial interest. There is no strong financial rationale for novel drug development without public or philanthropic support.

• Regulatory and/or policy challenges to approval

  New veterinary drugs in the EU must meet EMA or national regulatory requirements, including GMP standards and safety data. Resistance risk in zoonotic pathogens is increasingly considered in regulatory assessments.

  GAPS

  Risk of inducing resistance mechanisms with potential impact on therapeutical drug effectiveness in humans needs careful consideration.

• Commercial feasibility (e.g manufacturing)

  Commercial feasibility depends on the cost and scalability of the drug candidate. Repurposing known drugs may reduce R&D expenses, but efficacy and safety for leishmaniasis must be demonstrated.

  GAPS

  The limited market size for canine leishmaniasis restricts investment. High costs of manufacturing under GMP conditions and uncertain IP ownership for repurposed compounds pose challenges. Feasibility of fixed-dose combinations has not been explored.

• New developments for diagnostic tests

• Requirements for diagnostics development

  Diagnostic development depends on both pathogen antigenic properties and host immune response profiles. Recent efforts focus on improving sensitivity to detect asymptomatic infections and achieving DIVA compatibility, particularly in dogs. Opportunities exist for low-cost, rapid, and field-deployable platforms such as isothermal amplification assays and recombinant antigen-based serology.

  GAPS

  Existing diagnostics lack the ability to detect early or subclinical infections with high sensitivity. DIVA-compatible tools are unavailable for veterinary use. There is limited development of robust, field-suitable formats adaptable to varied endemic conditions and sample types. Host-related factors influencing diagnostic performance are underexplored.

• Time to develop new or improved diagnostics

  Estimation 2 years.

  GAP

  Time estimates often overlook the duration required for multicenter field validation, regulatory harmonization, and scale-up. Molecular assays may require longer due to technical complexity and training requirements for end-users.

• Cost of developing new or improved diagnostics and their validation

  Serological tests are generally lower-cost, while molecular or multiplexed assays require greater investment due to reagents, equipment, and field validation.

  GAPS

  Cost structures for veterinary diagnostics are poorly documented. There is little economic modeling of affordability and return on investment, especially in low-resource settings. High validation and regulatory costs limit innovation in the veterinary sector.

• Research requirements for new or improved diagnostics

  This largely depends on the type of diagnostics.

  GAPS

  No validated markers currently exist to predict progression or infectivity. Differentiating exposed from infectious animals remains a major challenge. There is a lack of standardization in defining infection stages, complicating tool validation and comparison.

• Technology to determine virus freedom in animals

  In practical terms, confirming complete parasite clearance in dogs is not routinely pursued, as most tools cannot detect very low parasitemia. Instead, clinical control and reduced infectivity are often the goals. Infectivity to sand flies is sometimes assessed experimentally.

  GAPS

  There is no reliable, standardized diagnostic to confirm parasite elimination. Xenodiagnosis is limited to research use. Surrogate indicators of non-infectious status are not validated. This complicates export certification and disease elimination strategies.

• New developments for vaccines

• Requirements for vaccines development / main characteristics for improved vaccines

  Several requirements should be considered for the development of a successful canine vaccine with broad applicability across the world. They include an unbiased clinical methodology for efficacy and safety evaluation. Indeed, in the past, several evaluations of canine vaccine candidates were performed using non-optimized experimental challenge models (e.g., insufficient numbers of experimental dogs) limiting the possibility for solid statistical analysis of data significance. This has led to some confusion on the true potential of some vaccine candidates. In addition, there is a need to further develop immunomonitoring laboratory tools to assess surogate markers of protection in dogs and to ensure that vaccine candidates are designed using a scalable industrialization platform. Development of a DIVA vaccine is a critical feature for a vaccine targeted at countries with an existing culling program of seropositive dogs (e.g. Brazil), but also in endemic EU countries due to interference with ongoing monitoring and surveillance activities on the spread of the disease.

  GAPS

  Several gaps currently limit the possibility to accelerate access to a successful canine vaccine with broad applicability. A relevant, reliable and affordable/accessible vaccine clinical evaluation methodology based on natural transmission of the infection (ideally in the target species). Better understanding of immune correlates of protection (biomarkers) in dogs and development/validation of the corresponding analytical technologies. Selection of a scalable manufacturing vaccine technology. Collectively all these aspects are critical for the development of an improved vaccine. Although several manufacturing technologies of interest are readily accessible, an appropriate clinical evaluation methodology and biomarkers remain critical unmet needs/gaps.

• Time to develop new or improved vaccines

  Developing a new or improved canine vaccine typically takes 5 to 10 years, depending on the maturity of the technology platform, availability of validated biomarkers, access to natural challenge models, and coordinated investment across stakeholders.

  GAPS

  Timelines can be delayed due to lack of standardized efficacy protocols and validated correlates of protection. Regulatory and logistical delays may further extend development. Limited pipeline diversity and public–private investment gaps contribute to prolonged R&D cycles.

• Cost of developing new or improved vaccines and their validation

  The estimated cost for developing a new canine leishmaniasis vaccine, including validation, is around €10 million. This includes early discovery, antigen production, preclinical studies, field trials, and regulatory approval steps.

  GAPS

  Cost estimates vary widely based on the platform, but no cost-effectiveness analyses exist for endemic vs non-endemic settings. The financial return on investment is uncertain, especially in low-income regions, limiting private sector interest. Public funding remains limited and fragmented.

• Research requirements for new or improved vaccines

  Research must integrate clinical efficacy models based on natural transmission, immune response monitoring, scalable production methods, and collaborative partnerships across academia, industry, and public agencies. Field trials with sufficient statistical power and endpoint standardization are essential.

  GAPS

  Major gaps include: lack of optimized canine challenge models using natural infection; absence of validated surrogate markers of immunity; limited understanding of host–pathogen–vector interactions; and insufficient investment in long-term cohort studies. Safety monitoring frameworks are also underdeveloped.

• New developments for pharmaceuticals

• Requirements for pharmaceuticals development

  There is a need for new drugs that offer parasitological cure, have minimal toxicity, and are easy to administer—ideally orally or topically. Existing therapies mostly result in clinical improvement, not parasite clearance. Treatment protocols are long and may require combination therapy.

  GAPS

  There is a lack of drugs targeting novel mechanisms or stages of the parasite. Canine-specific pharmacokinetics are under-researched. Current treatment options do not prevent relapse or reduce transmission. Opportunities for host-directed or immunomodulatory therapies remain unexplored.

• Time to develop new or improved pharmaceuticals

  The time required to develop a new pharmaceutical product is highly variable, but typically ranges from 8 to 12 years. This includes compound discovery, target validation, preclinical studies, safety testing, clinical evaluation, and regulatory approval.

  GAPS

  Few pharmaceutical candidates have entered veterinary development pipelines. There are no fast-track or harmonized regulatory pathways for anti-leishmania drugs in dogs. The absence of defined efficacy endpoints slows trial design and delays timelines.

• Cost of developing new or improved pharmaceuticals and their validation

  Financial rationale for a new CanL pharmaceutical development is questionable.

  GAP

  Market attractiveness for a new CanL therapeutical is limited due to already licensed products and to the wide off-label use of several unlicensed drugs.

• Research requirements for new or improved pharmaceuticals

  Research should focus on discovering parasite-specific targets that do not overlap with human drugs to prevent cross-resistance. In vivo canine models mimicking chronic natural infection are essential for efficacy testing. Combination therapies and novel delivery systems, such as topical or transdermal drugs, are under early investigation. Biomarkers of therapeutic response are beginning to be explored.

  GAPS

  Identification of novel targets not shared with human therapies to avoid resistance overlap. Development of in vivo models in dogs that reflect natural transmission and chronic infection. Combination therapy studies to reduce treatment duration and relapse. Development of topical/transdermal formulations for better compliance. Validation of biomarkers for therapeutic response in dogs

Disease details

• Description and characteristics

• Pathogen

  Leishmaniasis is not a single disease but represents a complex spectrum of diseases caused by intracellular protozoan parasites belonging to the Leishmania species and transmitted by blood-sucking female phlebotomine sand flies. The flagellated forms (promastigotes) are transmitted by the bite of the vector and multiply as aflagellated forms (amastigotes) within cells of the mononuclear phagocyte system. Each parasite species circulates in natural foci of infection where susceptible phlebotomines and mammals coexist. The epidemiology and clinical manifestations of the diseases are largely diverse, being usually grouped into 2 main entities: zoonotic leishmaniases, where domestic or wild animal reservoirs are involved in the transmission cycle and humans play a role of an accidental host, and anthroponotic leishmaniases, where man is the sole reservoir and source of vector’s infection. Clinically, leishmaniases are broadly divided into systemic forms (visceral leishmaniasis, VL) and cutaneous/mucocutaneous forms (CL/MCL).

  GAPS

  The molecular and virulence factors that determine tissue tropism (dermotropic vs viscerotropic species) are poorly understood. The biological interactions between parasite, host, and vector remain under-characterized. Diagnostic differentiation among Leishmania species in mixed-endemic areas is often lacking, limiting targeted intervention.

• Variability of the disease

  Each nosogeographical entity of leishmaniasis is characterized by a specific pathogen, a main reservoir host and one or more - closely related - species of phlebotomine vectors. About 20 named Leishmania species and subspecies are pathogenic for humans, and 98 sand fly species are proven or suspected vectors. Molecular taxonomy studies suggest that Leishmania species are indeed a complex of close-related genotypes which may differ in the clinical outcome of the infections (e.g. some strains of L. infantum may cause VL, others CL in humans). Being eukaryotic organisms, variability and mutations are not expected to occur during short timescales, although drug pressure can select drug-resistant parasites transmissible in nature (e.g. antimony resistance in Indian L. donovani). Most of leishmaniasis entities are zoonotic by nature and reservoir hosts are usually wild mammals. Zoonotic VL, a severe disease of humans, represents the most widespread and sole entity characterized by a domestic reservoir host, the dog. L. infantum (syn. L. chagasi) is the agent which causes a severe chronic disease in dogs (canine leishmaniasis, CanL) over a wide geographical range: Mediterranean basin, Middle East, parts of Central Asia and China, where the disease is transmitted by Phlebotomus sand flies of the subgenus Larroussius; and in Latin America, mainly Brazil, where the vector is Lutzomyia longipalpis. Other leishmaniasis entities with major impact on human health include anthroponotic VL, caused by L.donovani in East Africa and the Indian subregion (vectors: P.martini, P.orientalis, P.argentipes; reservoir: humans); anthroponotic CL, due to L.tropica in north Africa and Middle East (vector: P.sergenti; reservoir: humans, but dogs and rock hyraxes may play a role of reservoir in some settings); zoonotic CL, caused by L. major in Africa, Middle East and Central Asia (vector: P.papatasi; reservoir: wild rodents); New World sylvatic CL/MCL, caused by several Leishmania species (e.g. L. mexicana, L. braziliensis, L. amazonensis, L. panamensis, etc.) transmitted by various Lutzomyia Nyssomyia, Psathyromyia, Psychodopygus and Verrucarum subgenera sand flies and hosted by a wide range of wild mammals. The role of dogs in the life cycle of L.braziliensis and L.peruviana is unclear.

  GAPS

  Molecular determinants of strain-specific pathogenicity are not fully characterized. The interaction between host genetics and clinical outcome requires further study. The ability of Leishmania species to adapt to new vectors and hosts under environmental pressures (e.g., climate change, urbanization) is poorly understood.

• Stability of the agent/pathogen in the environment

  By itself the parasite is unstable in the environment but the leishmaniasis foci, representing particular biotopes, are stable whenever conditions for the sand fly vector and the reservoir host are appropriate. There is no evidence that contaminated biotopes are able to clear themselves spontaneously from the infection. In contrast, there is evidence of infection and disease emergences in new biotopes and species over the last decade.

  GAPS

  Mechanisms underlying recent northward spread of the canine infection in the EU are not fully understood. Ability to predict canine incidence remains limited. The mechanisms involved in the persistence of anthroponotic VL during interepidemic periods (especially in the Indian subcontinent) remains poorly understood. Do humans with chronic post-kalazar dermal leishmaniasis (PKDL) represent a significant reservoir for anthroponotic VL? There is also a need to elucidate the role of some domestic ruminants, and especially goats, as potential secondary reservoirs. Along the same lines, it will be necessary to further explore the role of dogs as part of the anthroponotic cycle of VL in Sudan. There is also the need to better understand the role of "deadend" livestock hosts in maintaining sand fly populations.

• Species involved

• Animal infected/carrier/disease

  As the important reservoir, domestic dogs are infected by L infantum in endemic areas. The prevalence of infection is variable but can be very high in some areas (up to 60% depending on the diagnostic method used). However, often the large majority of infections remain subpatent or asymptomatic for a long time before eventually becoming patent and symptomatic. Therefore, symptomatic patent disease is often limited to a smaller proportion of dogs in cross-sectional population studies. Some dogs are able to control spontaneously the infection and - potentially - to eliminate it. Although infection with L infantum is reported in cats and (exceptionally) in horses, there is no evidence that these species act as reservoirs for human or canine infection. Cat appears to be susceptible to the infection, but clinical expression appears limited and inconsistent in this species. Likewise, wild canid (wolf, fox and jackal) populations can show similar infection rates as in dogs, however the prevalence of progressive clinical signs in these species is substantially lower, consequently they may not be as infectious as dog populations to support a primary transmission cycle.

  GAPS

  The role of infected prepatent dogs in zoonotic VL infection transmissibility remains poorly understood e.g. the parasitaemia threshold in dogs required for parasite transmission to the sand fly vector is unknown. Factors determining the ratios of prepatent, asymptomatic patent and symptomatic patent infections are not well understood; ratios will depend on the analytical tools used to quantify infections. The relative importance of immune-based protection vs. genetic resistance in dogs is poorly understood. See also below

  It will be necessary to explore the potential role of cats in the epidemiology of L. infantum.

  The role of wildlife as potential reservoirs of Leishmania spp. remains poorly understood and requires further investigation to assess their contribution to transmission cycles

• Human infected/disease

  Human infection with L. infantum or L. donovani can lead to severe systemic disease (VL) which is usually lethal in the absence of therapy. In several areas (e.g. Mediterranean countries) strains of L. infantum can also cause CL or TL lesions. The number of asymptomatic infections is overwhelming as compared to symptomatic patent infections in humans, with reported ratios ranging from 1:4 to 1:50 or lower. As previously described, humans are also susceptible to several other Leishmania species leading to a spectrum of clinical diseases.

  GAPS

  The factors (e.g. genetic, immunological, environmental) that govern human infection outcomes (e.g. asymptomatic, progressive and carrier state), requires further multidisciplinary studies. The impact of emerging forms of immunosuppression, such as organ transplantation and the use of biologic therapies, on susceptibility to leishmaniasis requires further investigation

• Vector cyclical/non-cyclical

  In temperate areas (Mediterranean basin, Middle East, Central Asia and China) the transmission of L. infantum occurs only during warm months, coinciding with the activity period of adult sand flies, but due to the variable and lengthy pre-patent period, seasonal variation in the disease incidence in dogs and humans may not be apparent. By contrast, in warmer regions such as much of endemic Brazil, sand fly activity and human and canine transmission of zoonotic VL is year round.

  GAPS

  Important parameters need to be elucidated, such as biological and environmental conditions that affect the sand fly fecundity, survival, dissemination, or host's relative abundance and distribution affecting human and canine transmission dynamics.

• Reservoir (animal, environment)

  Dogs are the primary reservoir for zoonotic VL due to L. infantum. InBrazil, it is thought that wildlife (e.g. foxes) is unable to maintain a transmission cycle independently of dogs. As previously described, a wide range of wild mammals (mainly rodents) are reservoirs of the other zoonotic entities of leishmaniasis, in different environments such as desert areas, steppe, rural settings, primary forest, etc.

  GAP

  The role of wildlife as reservoir for L. infantum around the Mediterranean basin and central Asia is not well understood but could be more significant than inBrazil. There are suggestions that additional zoonotic hosts could be secondary reservoirs of L. infantum (e.g. cats) and L. donovani (e.g. goats). Should these be confirmed, the classical transmission cycles of these parasite(s) may need to be revisited with implications for prevention and control strategies. This could be significant during inter-epizootic periods. The presence of fox hound infections in theUS is still poorly understood and further investigations on the role of local sand flies or alternative modes of transmission are warranted. Which populations and/or species of rodent are significant reservoirs of L. braziliensis requires xenodiagnosis population studies.

• Description of infection & disease in natural hosts

• Transmissibility

  Natural transmission of Leishmania occurs exclusively by the bite of infected phlebotomine sand flies. In zoonotic VL it has been suggested that dog-to-dog transmission may occur in some circumstances.

  GAPS

  Although symptomatic patent infections play an important role in infection transmission, the role of prepatent or asymptomatic patent infections in transmission is less well understood. There are suggested putative non-sand fly-based transmission routes of fox hound infection in the US. The parasite-sandfly-host immunological interactions governing successful parasite establishment and transmission remains poorly understood.

• Pathogenic life cycle stages

  The infectious metacyclic promastigote stage is transmitted to the mammalian host via the sand fly bite and differentiates into amastigotes within macrophages. These intracellular forms replicate and disseminate within the host. During a blood meal, sand flies ingest amastigotes that transform and multiply in the gut before becoming infectious promastigotes again.

  GAPS

  Intermediate developmental stages in the sand fly and their implications for transmission efficiency are not fully characterized. The localization and replication dynamics of amastigotes within different host tissues remain poorly quantified.

• Signs/Morbidity

  Symptomatic patent infections in dogs are typically attributed to a combination of skin/cutaneous and visceral pathologies. In dogs, many of these clinical signs are not specific and may vary in intensity and kinetics. In the absence of therapy, symptomatic patent infections are almost always lethal, and relapses to canine patent infection post treatment are common. Symptomatic patent infections in dogs are typically attributed to a combination of skin/cutaneous and visceral pathologies. In dogs, many of these clinical signs are not specific and may vary in intensity and kinetics. In the absence of therapy, symptomatic patent infections are almost always lethal, and relapses to canine patent infection post treatment are common.

  GAPS

  There is no consensus on clinical staging. Predictors of progression from subclinical infection to overt disease are lacking. The pathogenesis of organ damage, especially renal and ocular involvement, is not fully understood.

• Incubation period

  The incubation period in dogs is highly variable, ranging from several weeks to over a year. Most infected dogs remain asymptomatic for long periods before clinical signs appear. Progression is influenced by the dog’s immune status, genetics, concurrent infections, and parasite load.

  GAPS

  Parameters influencing the duration of the incubation period are unknown. Overall health and nutritional status, genetic background, inoculum load, and the effects of confounding infections, to name a few, are suspected to play a role.

• Mortality

  Without treatment, visceral leishmaniasis in both humans and dogs has a high mortality rate. In dogs, progression to renal failure is a common cause of death. Cutaneous forms are generally non-fatal and often resolve spontaneously, although healing can be slow and disfiguring.

  GAPS

  Infection-induced population mortality rates are important demographic values for mathematical modelling, but which, especially for canine VL, remain uncertain due to the non-specific signs of this disease and normal absence of differential diagnosis.

• Shedding kinetic patterns

  Parasites are not spontaneously shed from natural infected hosts.

  GAP

  Role of vertical transmission is poorly understood but may play a role in fox hound infections in parts of the US.

• Mechanism of pathogenicity

  Largely dominated by immunopathologies. In dogs, the severity of signs (renal, ocular, cutaneous, etc) is associated to the abnormal secretion of immunoglobulins which deposit on the blood vessel's endothelium to form immunocomplexes. In humans, the exacerbatory contribution of IL-10 is well established in the development of the visceral form of the disease. Similarly in murine models of L. major, the role of IL-4 and IL-13 in exacerbatory CL disease is relatively well understood. Marked cutaneous delayed hypersensitivity, exuberant lymphoproliferation and mixed Th1 and Th2 cytokine responses characterize MCL presentation. Polymorphism in TNF-a promotor sequences has been associated with mucosal leishmaniasis.

  GAPS

  The precise mechanisms underlying immunopathologies in dogs and humans are not fully understood. Whether similar physiopathological mechanisms are involved in canines and humans is suspected but not definitively established.

• Zoonotic potential

• Reported incidence in humans

  About 1.3 million new cases of human leishmaniases (0.3 million visceral) are considered to occur every year in the endemic zones of Latin America, Africa, the Indian subcontinent, the Middle East, Central Asia, China, and the Mediterranean region. Overall estimated prevalence is 12 million people with Disability Adjusted Life Years burden of 2 million. Among different entities of the disease, it is estimated that clinical cases of zoonotic VL amount to 1,500 - 2,000/year in the Mediterranean basin and Middle East, and some 5,000 cases in Latin America. These statistics are expected to be underestimates due to significant under reporting (see below).

  GAPS

  Accurate incidence data are lacking in many endemic regions due to poor reporting systems, inconsistent case definitions, and limited diagnostic access. Subclinical and atypical presentations further complicate surveillance.

• Risk of occurence in humans, populations at risk, specific risk factors

  Zoonotic VL due to L. infantum affects essentially infants throughout its endemic range, with variable incidences. Adults are less at risk unless exposed to immunosuppressive conditions such as HIV co-infection or drug treatments after transplant or prescribed to cure immunopathological disorders. Other risk factors include famine, malnutrition, mass migration, civil disturbance, poor economic conditions, and crowding. The proximity to an infected person is a major risk factor for anthroponotic VL and CL, and proximity to infected dogs is a risk factor for both human and canine zoonotic VL infection. Zoonotic VL due to L. infantum affects essentially infants throughout its endemic range, with variable incidences. Adults are less at risk unless exposed to immunosuppressive conditions such as HIV co-infection or drug treatments after transplant or prescribed to cure immunopathological disorders. Other risk factors include famine, malnutrition, mass migration, civil disturbance, poor economic conditions, and crowding. The proximity to an infected person is a major risk factor for anthroponotic VL and CL, and proximity to infected dogs is a risk factor for both human and canine zoonotic VL infection.

  GAPS

  The significance of livestock ownership patterns in ‘zooprophylaxis’ (reducing transmission) or ‘zoopotentiation’ (increasing transmission) has not been adequately researched. The relative contribution of environmental, genetic, and immunological risk factors is not well defined. The impact of urbanization on human-vector contact is under-studied. The role of livestock in either increasing (zoopotentiation) or decreasing (zooprophylaxis) human risk remains inconclusive.

• Symptoms described in humans

  Visceral disease includes anaemia, splenomegaly and fever. The clinical incubation period is 4-6 months on average. Death is the usual outcome in the absence of therapy. In HIV-co-infected patients, the symptomatology is more polymorphic. The onset of clinical disease associated with anthroponotic VL is sometimes fulminant (i.e. sudden and severe) leading to rapid death. The cutaneous disease consists of nodular or ulcerative lesions which tend to resolve spontaneously in a variable period of time. In mucosal disease, which may develop from CL lesions caused by L. braziliensis and L.panamensis, parasitic metastasis occur in the nasal mucosal that eventually extends to the oropharynx and larynx. MCL evolves slowly and does not heal spontaneously.

  GAPS

  The clinical spectrum in immunocompromised patients is not well described. Early detection is complicated by nonspecific symptoms. The pathophysiology and transmission potential of post-kala-azar dermal leishmaniasis (PKDL) remain incompletely understood.

• Likelihood of spread in humans

  The link between the canine reservoir and human VL due to L. infantum is well established throughout its distribution. The role of dogs in other Leishmania species cycles is unclear.

  GAP

  A detailed understanding of the link between the canine reservoir and human epidemiology in East Africa and for L. tropica around the Mediterranean basin and centralAsia is still limited.

• Impact on animal welfare and biodiversity

• Both disease and prevention/control measures related

  In the absence of therapy, canine leishmaniasis is a severe lethal disease in dogs. Sick dogs will express both cutaneous and visceral clinical signs and they experience severe body weight losses overtime. The levels of stress associated with the disease in dogs is important. Existing prevention methods (insecticides) have no known negative impact on animal welfare. In contrast, some of the commonly used therapies are associated with significant side effects and toxicity. No known impact on biodiversity. The ethicality of dog culling methods (in parts of Brazil) remains a serious issue.

• Endangered wild species affected or not (estimation for Europe / worldwide)

  According Brazilian law, euthanasia of infected dogs is mandatory, but since 2017 in some areas it is now possible to treat infected dogs. No culling policy is in place in the rest of the world.

  GAPS

  The impact and ethical acceptability of mandatory culling policies are controversial and insufficiently studied. Alternative strategies, such as mass vaccination or insecticide-based prevention, may offer more sustainable outcomes but require comparative evaluation.

• Slaughter necessity according to EU rules or other regions

  According Brazilian law, euthanasia of infected dogs is mandatory, but since 2017 in some areas it is now possible to treat infected dogs. No culling policy is in place in the rest of the world.

• Geographical distribution and spread

• Current occurence/distribution

  In countries of the Mediterranean basin and in some parts of Brazil up to 60% of the dogs have serological signatures of exposure to the parasite. In southern Europe (Italy and Spain) there is evidence of recent northward spreading of zoonotic VL, from coastal Mediterranean to continental climates. L. infantum is probably now endemic in southern Germany. In Brazil, zoonotic VL has expanded its range from a typically rural disease to a peri-urban/urban focus over the last several decades. Because these endemic areas have a high population density, larger human and canine populations are now at increased risk. Limited outbreaks in fox hounds have been reported in several states of the US, but the mode of transmission is unclear.

  GAPS

  Surveillance is incomplete in many endemic areas, and environmental drivers of distribution remain poorly characterized. The role of human-mediated dog movement in spreading infection is under-investigated. An understanding of the importance of infection and clinical expression in cats and horses remains minimal at this stage. Multivariate environmental and climatic features that significantly affect the geographical spread of sand flies and canine transmission are still poorly understood

• Epizootic/endemic- if epidemic frequency of outbreaks

  Zoonotic VL is endemic in dogs with a sporadic pattern in humans (no epidemics reported in the past decades). In humans, epidemic modes are only described for anthroponotic VL in Indian subcontinent and East Africa (outbreaks apparently occurring at around 10-year intervals) and for Old World zoonotic CL in northern Africa and Middle East, mostly associated to land reclamation in biotopes where infected rodents live.

  GAPS

  The mechanisms underlying the persistence of the infection in between epidemic outbreaks of anthroponotic VL in Indian subcontinent and East Africa has received limited investigation at this stage. Mathematical models that capture the epidemiological patterns are needed.

• Speed of spatial spread during an outbreak

  In dogs the epidemiology is essentially endemic. Human outbreaks of anthroponotic VL and zoonotic CL may involve new infections across large regions and territories within relatively short time frames.

  GAPS

  Quantitative estimates of disease spread in dogs or vectors are lacking. The role of long-distance canine movement in dissemination has not been systematically assessed. Transmission models rarely incorporate realistic mobility patterns.

• Transboundary potential of the disease

  Traditionally, cooler temperatures and reduced vector activity season have limited infection/disease spread northward of the canine disease in the EU. Global warming is likely to have an impact at this level (see above). Geographical spreading could also be related to vector dissemination linked to human activities (transport, travel) although long range (inter-continental) dispersion is unlikely because sand flies are not as robust as some mosquitoes and are not known to be wind-dispersed (as for instance Culicoides). There is direct evidence for the introduction to Northern EU of L. infantum in dogs taken to Southern EU on holidays or rescued from there as strays. Importation of non-endemic Leishmania species is frequent among immigrants or tourists. Of special concern are those anthroponotic species (L. donovani and L. tropica) which may find suitable vectors (specific or permissive) in southern EU (f.i. L. donovani transmitted by Larroussius sand flies in Cyprus; L. tropica by P. sergenti in Sicily). L. infantum is thought to have been introduced originally into the New World by dogs infected in the Old World.

  GAPS

  There is limited real-time monitoring of cross-border infections in dogs or humans. The capacity of non-traditional vectors to support transmission in new regions is under-studied. Regulatory inconsistencies in dog travel and diagnostics create control gaps.

• Route of Transmission

• Usual mode of transmission (introduction, means of spread)

  Natural transmission of Leishmania occurs exclusively by the bite of infected phlebotomine sand flies. In zoonotic VL e.g. in US fox hounds it has been suggested that dog-to-dog transmission may occur in some circumstances.

  GAPS

  The quantitative dynamics of transmission (e.g., parasitemia thresholds, biting efficiency, and EIP variability) are not well understood. The relative importance of alternative transmission routes under natural conditions is poorly documented

• Occasional mode of transmission

  Sporadic reports of congenital transmission of VL in humans are consistent with some confirmation in experimental puppies. Additional transmission routes include blood transfusions, organ transplantations, and sexual transmission in humans. Transmission through shared infected syringes has been reported amongst IV-drug users in Southwest Europe.

  In some dogs (fox hounds) occasional transmission through bites is considered to play a role (essentially in the US).

  GAPS

  The prevalence and epidemiological relevance of non-vectorial transmission routes remain unclear. There is limited surveillance of blood donors or organ recipients in endemic areas. More data are needed to assess risks in veterinary clinical practice and breeding programs.

• Conditions that favour spread

  Outdoor activity of hosts during peak sand fly biting times (particularly at dusk and sunrise). Increased travelling of dogs to southern EU (holidays, second homes) also increases infection spread. In humans, immunosuppression is clearly a risk factor. In Brazil, most transmission appears to be peri-domestic and potentially also inside houses. Migration and crowding are typical conditions favouring spread of anthroponotic agents (L. tropica and L. donovani). Generally, factors affecting increased densities of vectors and mammalian reservoir hosts. See also above.

  GAPS

  The large number of refugees in EU from countries with different Leishmania species are likely to spread the pathogen especially in Mediterranean countries where vectors of Leishmania are abundant. The role of stray dogs must be investigated mainly in endemic areas.

• Detection and Immune response to infection

• Mechanism of host response

  The host immune response to Leishmania is heterogeneous. Asymptomatic or self-resolving infections are associated with strong cellular (Th1-type) immunity, particularly IFN-γ production. In contrast, progressive disease is characterized by humoral dominance, polyclonal B-cell activation, and immunopathological responses. Cellular anergy is typical in severe VL.

  GAPS

  The mechanisms underlying the transition from protective to pathogenic immune profiles are poorly defined. The roles of IL-10, regulatory T cells, and chronic immune activation are under investigation. Comparative immunological profiling across host species is limited. No validated immune-based staging systems exist.

• Immunological basis of diagnosis

  In dogs and humans affected by zoonotic VL, and in humans affected by anthroponotic VL, disease progression is usually associated with detectable high titre anti-Leishmania humoral responses while resistance appears to be associated with cellular immunity, measured by a leishmania-specific skin test or by quantification of one or more surrogate cytokine markers. In human CL, humoral responses are very limited unless mucosal tissues are involved (e.g. in MCL).

  GAPS

  In dogs and humans affected by zoonotic VL, and in humans affected by anthroponotic VL, disease progression is usually associated with detectable high titre anti-Leishmania humoral responses while resistance appears to be associated with cellular immunity, measured by a leishmania-specific skin test or by quantification of one or more surrogate cytokine markers. In human CL, humoral responses are very limited unless mucosal tissues are involved (e.g. in MCL).

• Main means of prevention, detection and control

• Sanitary measures

  Sanitary measures are largely diverse depending on the nosogeographical entity of leishmaniasis. As regards zoonotic VL, massive destruction of dogs had been practiced in endemic foci of China in the past, with some results. Culling of seropositive dogs has been implemented in Brazil but has had very limited efficacy to reduce the prevalence of either canine or human diseases, likely because of low owner compliance, insensitive diagnostic tests, long delays to dog removal, and high replacement rates with susceptible dogs. Active case detection and drug treatment of infected individuals are the recommended measures in both zoonotic and anthroponotic forms of leishmaniasis (e.g. VL elimination programme in the Indian subcontinent).

  GAPS

  Need for controlled, replicated and appropriately powered intervention trials to test different dog removal strategies. Logistics, ethical and animal welfare aspects are serious limitations to dog culling programs.

• Mechanical and biological control

  Fine mesh nets are the most effective mechanical measure to prevent sand fly bites on humans indoors, but are not expected to impact on zoonotic transmission cycles where humans are not a reservoir. Also, large scale control of vectors by spraying insecticides is only expected to be effective when sand flies are accessible (i.e. when transmission occurs peridomestically) and blood-fed flies rest indoor (endophilic behaviour). Therefore, in endemic EU epidemiological conditions, insecticide spraying is expected to be of low cost-effectiveness. In this context, insecticide-impregnated bednets are not considered a practical option to control zoonotic VL but have demonstrated some (variable) efficacy against anthroponotic CL and VL. In dogs, individual transient protection is possible using topical insecticides (3-4 weeks efficacy) or insecticide-impregnated collars (6-month efficacy).

  GAPS

  Need for controlled, replicated and appropriately powered intervention trials to test different spraying strategies and formulations. Transient protection of individual dogs is possible using topical insecticides or repellent-impregnated collars but a longer-term solution with much broader applicability is required for disease prevention/control of larger dog populations to impact on the zoonotic VL transmission cycles. Compliance in the developing world will largely depend on the availability of low cost products.

• Diagnostic tools

  Demonstration of parasites in smears/imprints of infected tissues or culture from the same material still represents the golden standard for leishmaniasis diagnosis worldwide, but is of low sensitivity. Different serology based diagnostic tests are available with good performance to assess clinical disease. However, sensitivity is not always sufficient to detect some asymptomatic (pre-patent and pre-progressive disease) stages that may have an important role in transmission. Molecular diagnostics (PCR) are also available but remain of limited sensitivity when performed on blood samples, and require relatively high levels of technical skill.

  GAPS

  Easy to use sensitive and specific diagnostic tools to detect pre-patent and pre-progressive stages of disease.

• Vaccines

  Vaccination is the most rational strategy to control the disease in dogs and could also be of interest to control anthroponotic forms of leishmaniasis in humans. A conventional vaccine (“leishmanization”) based on live attenuated parasites was in use for humans to prevent some forms of the cutaneous disease in Middle East and Central Asia, but is no longer recommended. A recombinant protein-based vaccine has demonstrated some protective potential in humans when combined with chemotherapy. A canine vaccine licensed only for use in Brazil has shown efficacy but is not widely adopted. In Europe there is one canine vaccines commercialized.

  GAPS

  No human vaccine exists despite decades of research. No vaccine provides sterilizing immunity or DIVA compatibility. Field data on vaccine coverage and transmission impact are scarce.

• Therapeutics

  Several therapeutic options exist for both humans and dogs including pentavalent antimonials, amphotericin B deoxycholate, liposomal formulations of amphotericin B, miltefosine and paromomycin. In general, human cases of VL or CL are successfully treated with cure rates exceeding 95% with some exceptions e.g. in the Indian subcontinent where 35% of VL patients are unresponsive to antimonials. Potential long-term improvements in cost and effectiveness are expected with the use of combined drug treatments. In contrast to the general trend in humans, dogs with patent and progressive disease are mostly unresponsive to, or relapse after, treatment. Despite the poor parasitological responses, anti-Leishmania therapy is commonly practiced in dogs in EU countries, which may lead to the spread of drug resistance.

  GAPS

  Need for new canine and human pharmaceutical options, and clinical trials of combined therapies.

  In EU these pharmaceutical options have to be different for dogs and humans in order to protect Public Health from drug resistant Leishmania species. Lack of systematic surveillance and standardized methodologies for monitoring antileishmanial drug resistance in both human and veterinary settings, hindering the early detection of resistance trends and the implementation of effective control strategies.

• Biosecurity measures effective as a preventive measure

  Due to the absence of airborne transmission and the need for a vector sand fly, biosafety requirements for Leishmania research are minimal.

• Border/trade/movement control sufficient for control

  Leishmania immunology status is required in some administrative regions of EU as a prerequisite to trade dogs to other EU countries.

  GAP

  Lack of DIVA-compatible vaccines and diagnostics undermines regulatory frameworks. No harmonized guidelines exist for dog movement across leishmaniasis-endemic and non-endemic regions.

• Prevention tools

  Insecticide residual spraying of houses and animal sheds against peridomestic vectors. Mechanical tools (fine mesh nets to prevent sand fly bites indoor), insecticide treated bed nets (ITNs) and topical insecticides to protect humans. In dogs, individual protection is also possible using topical insecticides (3-4 weeks duration) and/or insecticide-impregnated collars (6-month duration). Insecticide-based products provide individual protection; community-wide application to dogs has been shown to impact on human and canine zoonotic VL infection incidence, whereas community-level provision of ITNs to protect humans is not expected to impact on zoonotic transmission cycles, whereas they have shown some success against anthroponotic Leishmania species.

  GAPS

  Need for controlled, replicated and appropriately powered intervention trials. Large scale and sustainable prevention based on canine topical insecticides currently face multiple logistic and socio-economic challenges (e.g. owner compliance, current costs, and short inter-intervention intervals). Sustainable long-acting compounds and formulations should be developed in conjunction with studies on effective delivery/public health education.

• Surveillance

  Research on CanL spatial distribution in EU and the Mediterranean region is increasing and made accessible online by the EC FP6 EDEN project. Another EU-funded project, LeishRisk (with WHO support) produced a compilation of peer-reviewed epidemiological literature. Seasonal dynamics of phlebotomine sand fly species proven vectors of Mediterranean leishmaniasis caused by L. infantum has been carried out between 2011-2013 under the frame of EU FP7 EDENext project.

  GAPS

  Public health and veterinary surveillance data remain fragmentary. More surveillance is necessary in Europe including better coordination of existing surveillance and linking human health, veterinary data, sand fly distributions and climate patterns. The monitoring of dog travel should continue to be improved and standardized. The existing notification systems provide only limited information and rarely differentiate between the zoonotic and anthroponotic forms of VL which may be particularly relevant where migration is prevalent. This is another factor that limits the ability to estimate the true importance of each form of the disease.

• Past experiences on success (and failures) of prevention, control, eradication in regions outside Europe

  Insecticide residual spraying of houses and animal sheds, and culling seropositive dogs in Brazil appears to have had limited impact on VL incidence. The latter practice is also questioned on ethical grounds. Reasons for failure include low owner compliance, insensitive diagnostic tests, long delays to dog removal, and high susceptible dog replacement rates. Setting up an effective control strategy for anthroponotic visceral leishmaniasis remains a challenge in endemic areas, as these are largely in the poorest countries of the world, in remote places and/or in complex settings (e.g. civil war in Somalia). In many endemic regions access to health care is logistically complex and treatment is not subsidised. Insecticide-impregnated bed nets have been used with some success against anthroponotic infections.

  GAPS

  Need for (1) controlled, replicated and appropriately powered intervention trials to test individual and integrated intervention strategies; (2) mathematical modelling to identify the sensitivity of transmission cycles to intervention approaches; (3) definition of veterinary and public health intervention goals (e.g. elimination or reduction in incidence?); (4) identification of effective implementation practices to sustain coverage (herd immunity).

• Costs of above measures

  The cost-effectiveness of culling dogs is low as culling requires house-to-house visits to screen dogs, expensive diagnostic kits and laboratories, and a revisit to remove positive dogs. Additional tests (and delay) may be required where owners dispute the initial results. Although the costs of insecticides to re-dip insecticide-impregnated bednets to prevent human leishmaniasis are low, investment on community education programs to sustain coverage are relatively high. Re-impregnation logistical issues have been partially overcome with the development of nets with long-lasting insecticide impregnation. Insecticide residual spraying is labour intensive and municipalities in developing countries have limited funds for regular blanket application. Current costs of the canine vaccine in Brazil are prohibitively expensive, as are costs of impregnated dog collars, thus neither are widely adopted for personal canine protection, particularly in poorer communities. Some municipalities have purchased collars for public distribution but without follow-up to monitor efficacy.

  GAP

  Comprehensive cost-effectiveness analyses of prevention strategies are scarce. Long-term economic modeling is needed to inform sustainable control policies.

• Disease information from the WOAH

• Disease notifiable to the WOAH

  Canine leishmaniosis is not officially listed as a notifiable disease by WOAH. However, it is considered a zoonosis of public health concern and is notifiable in some national surveillance systems, such as in Brazil and parts of the European Union.

  GAP

  The absence of a global notifiable status may hinder coordinated international surveillance and response. Standardized criteria for reporting and classification are lacking across countries.

• WOAH disease card available

  Direct links to the WOAH

• WOAH Terrestrial Animal Health Code

  Direct links to the WOAH

• WOAH Terrestrial Manual

  Direct links to the WOAH.

• Socio-economic impact

• Zoonosis: impact on affected individuals and/or aggregated DALY figures

  The leishmaniasis burden (all entities) is calculated at 2 090 000 disability adjusted life years (1 249 000 in men and 840 000 in women).

  GAPS

  DALY estimates are likely underestimated due to underreporting and lack of integration of long-term disability from cutaneous and mucosal forms. Burden stratification by age, gender, and region is incomplete in global metrics.

• Zoonosis: cost of treatment and control of the disease in humans

  First-line treatment for VL in humans (antimonial drugs) is expensive and needs to be administered parenterally by trained personnel. Treatment-cycle costs range from US$ 30 (for generic sodium stibogluconate) to US$ 120 (for meglumine antimonate) or US$ 150 (for sodium stibogluconate). In the case of relapse, patients need to be treated with a far more toxic second-line medicine, such as conventional amphotericin B (US$ 60) or pentamidine (US$ 70). Liposomal amphotericin B, currently the first-line choice in EU and the USA, requires short treatments by i.v. route, is highly effective and almost not toxic but is unaffordable in developing countries (US$ 1500 or more). Injectable paromomycin costs US$ 10. The first oral treatment, miltefosine, costs US$ 150 or more. There are no established treatments for CL or MCL; the most common are intralesional injection of antimonials, local cryo- or heat therapy, or parenteral administration of drugs used for VL, depending on the number and site of lesions. Costs can be extremely variable.

  GAP

  There is the need for controlled studies designed to test treatment efficacy for tegumentary leishmaniasis worldwide.

• Direct impact (a) on production

  There is no estimation of the impact on livestock. The clinical expression of the disease is restricted to dogs and humans, the impact - if any - can only be indirect.

  GAP

  Need to better understand the economic consequences of L. donovani infections in ruminants in endemic settings of anthroponotic VL.

• Direct impact (b) cost of private and public control measures

  In endemic countries that implemented specific programs for the control of leishmaniasis, public budget is allocated for human diagnosis and treatment, and insecticides and bednets for vector control. In most of the endemic countries, however, measures are integrated with those of other transmissible diseases, and free treatment of human patients is usually available at health centres or hospitals. Where treatment is not provided for free, private loans (with/without disproportionate interest charges) are sought with immeasurable impact on case families.

  In some countries endemic for zoonotic VL diagnosis of dogs is encouraged at public reference centres with reduced costs for the owners. No country endemic for zoonotic VL provides for free tools for the prevention of leishmaniasis in dogs (topical insecticides, collars), nor therapies.

  GAP

  Need for actions to facilitate diagnosis, treatment and prevention access of the poor to reduce direct and indirect impacts.

• Indirect impact

  Human VL is essentially a disease affecting the poorest population, for whom the infection contributes to the further propagation of poverty, because treatment is expensive and hence either unaffordable or imposing a substantial economic burden, including loss of wages. Loss of labour (due to leishmaniasis), and the need of workforce replacement may also represent an economic impact.

  GAP

  Human patients in developing countries have to overcome major logistic problems in order to access treatment: long distances to the treatment centre, lack of transport, treatment is unaffordable, or its costs pose a serious financial burden. For these reasons, patients may not comply with treatment (if they began) and drug resistance may emerge. There is a shortage of information on the actual cost of leishmaniasis, although it is known that in some parts of Asia, a family in which there is a case of leishmaniasis is three times more likely than an unaffected family to have sold its cow or rice field, plunging it into a vicious circle of disease-poverty-malnutrition-disease.

• Trade implications

• Impact on international trade/exports from the EU

  Leishmaniasis does not currently trigger formal international trade restrictions under WOAH or WTO frameworks. However, countries may impose import health requirements or voluntary testing recommendations for dogs originating from endemic areas.

  GAPS

  There is no global consensus on the testing, certification, or quarantine requirements for animals moving from leishmaniasis-endemic to non-endemic countries. A lack of harmonized guidance creates variability and potential trade uncertainty.

• Impact on EU intra-community trade

  EU legislation does not currently require testing for leishmaniasis in dogs moving between member states. However, local authorities or private carriers may impose additional requirements, especially in high-risk areas or when importing rescue dogs.

  GAPS

  The lack of DIVA-compatible vaccines complicates interpretation of serological tests in vaccinated dogs. There is no harmonized EU policy on movement of leishmania-exposed or vaccinated animals, which may lead to inconsistent enforcement.

• Impact on national trade

  National regulations vary widely. In Brazil, infected dogs may be subject to movement restrictions. In Europe, leishmaniasis status is not legally regulated for internal trade, but testing is sometimes requested by breeders, shelters, or adopters.

  GAPS

  The lack of national trade standards leads to inconsistent practices and gaps in disease control. There is a need for clearer guidance on movement, disclosure, and testing of animals for trade or adoption purposes, especially when vaccination confounds diagnosis.

• Links to climate

  Seasonal cycle linked to climate

  In the Mediterranean basin exposure to infected sand flies is higher during the summer months, but due to the variable and lengthy pre-patent period, seasonal variation in the prevalence (cf. incidence) of the disease in dogs and humans may not be apparent. By contrast, in warmer regions such as much of endemic Brazil, sand fly activity and human and canine transmission of zoonotic VL is year round. There are no reliable historical data to test the effects of climate change on leishmaniasis cycles.

  GAPS

  The effects of climate and climate change on transmission dynamics over longer timescales requires systematic and standardized longitudinal monitoring.

• Distribution of disease or vector linked to climate

  Temperature affects the development time and overwintering of sand flies and the extrinsic incubation period which is likely to be reflected in their duration of infectiousness.

  GAP

  Investigation of the vectorial capacity of traditionally non-vectorial sand flies in new foci or under different climatic conditions e.g. in Northern EU.

• Outbreaks linked to extreme weather

  Vector survival is limited in extreme weather.

• Sensitivity of disease or vectors to the effects of global climate change (climate/environment/land use)

  Climate change might impact zoonotic VL distribution directly (shortening of larval development or the extrinsic incubation periods) or indirectly (effect on the range and seasonal abundances of sand flies, extension of the breeding season increasing the risk of exposure for susceptible hosts). See also above

  GAP

  Historical data are scarce to provide compelling evidence of the impact of climate changes on sand flies and disease distribution in the EU.

• Main perceived obstacles for effective prevention and control

  The lack of a vaccine that is simultaneously effective, safe, affordable, DIVA-compatible, and capable of blocking transmission is the main technical obstacle to prevention and control of zoonotic visceral leishmaniasis. Canine vaccines available in Europe and Brazil do not prevent infection or parasite transmission and require annual boosters. Insecticide-based vector control is underused due to cost and compliance challenges. In many endemic regions, logistical barriers hinder delivery of insecticide spraying and dog-based interventions. Community education and engagement strategies are often absent. Diagnostics lack sensitivity for asymptomatic stages, and no standard tools exist to measure infectivity. Surveillance systems for dogs and vectors are weak or fragmented. Dog movement and international adoption remain largely unregulated.

  GAPS

  Critical gaps include the absence of reliable challenge models (especially those based on natural sand fly transmission), validated surrogate immune markers in dogs, and DIVA-compatible vaccines and diagnostics. No tools currently exist to detect infectivity or distinguish vaccinated from infected animals in the field. Surveillance systems for canine leishmaniasis are disconnected from human and vector data. Economic evaluations of interventions (vaccines, collars, culling) are rare, and implementation feasibility is poorly understood. The international movement of dogs, often without screening, poses a continuous risk for transboundary spread, and no harmonized policies exist to mitigate this.

• Main perceived facilitators for effective prevention and control

  Successful prevention and control of leishmaniasis depend on coordinated, cross-sectoral collaboration under a One Health approach. Translational research networks that combine expertise from parasitology, immunology, diagnostics, vaccine development, entomology, and public health are key facilitators. EU-supported initiatives and public-private partnerships have shown potential to accelerate innovation. The availability of recombinant vaccines (e.g., LetiFend®), scalable diagnostic technologies, and community-based vector control programs offer practical intervention tools. Enhanced awareness among dog owners and veterinarians in Europe has improved early detection and prevention. In some regions, municipal programs have piloted large-scale distribution of insecticidal collars or provided subsidized treatment for infected dogs.

  GAPS

  Despite growing scientific capacity, current facilitators are undermined by fragmented coordination, underutilization of digital platforms, and poor translation of research into field-scale implementation. There is no unified governance mechanism linking veterinary and human leishmaniasis control strategies. Communication tools, surveillance platforms, and response systems remain disconnected between sectors. Limited investment in local manufacturing capacity and the absence of sustainable funding mechanisms hinder long-term success. Lack of harmonized DIVA-compatible regulatory frameworks reduces the applicability of technological advances in movement control or trade certification. Community education and engagement programs are not systematically embedded in control strategies.

Risk

• About 2 million new cases of human visceral leishmaniasis are considered to occur every year in the endemic zones of Latin America, Africa, the Indian subcontinent, the Middle East, Central Asia, China, and the Mediterranean region. Public health and veterinary surveillance data remain fragmentary and these statistics are expected to be underestimates due to significant under-reporting.

  In humans, risk factors include famine, malnutrition, mass migration, civil disturbance, poor economic conditions, and crowding. Proximity to infected dogs is a risk factor for both human and canine zoonotic VL infection. Cooler temperatures and a reduced vector activity season have limited the spread of infection northwards in the EU but global warming is likely to affect the distribution of zoonotic VL.

  Vector control is difficult and insecticide spraying and the use of insecticide-impregnated bednets are not considered practical options to control zoonotic VL. In dogs, transient protection is possible using topical insecticides or insecticide-impregnated collars and community-wide application to dogs has been shown to impact on human and canine zoonotic VL incidence. Active case detection and drug treatment of infected individuals are recommended measures in both zoonotic and anthroponotic forms of leishmaniasis.

Main critical gaps

Conclusion

• Conclusion summary (s)

  Leishmaniasis represents a globally significant parasitic disease with major public and veterinary health implications, particularly in regions where Leishmania infantum is endemic and maintained through canine reservoirs. Despite notable advances in research and the availability of preventive tools such as vaccines, insecticidal collars, and diagnostic tests, these measures have only partially mitigated disease transmission or burden. Current vaccines do not confer sterilizing immunity or interrupt parasite transmission, and DIVA-compatible technologies are still lacking. Diagnostics remain insufficiently sensitive for detecting asymptomatic or prepatent infections, especially in dogs.Moreover, surveillance systems are fragmented, particularly across the veterinary and entomological sectors, and often disconnected from human health programs. Vector control is inconsistently applied and difficult to sustain, particularly in resource-limited settings. The movement of infected dogs—often unregulated—poses a persistent transboundary risk. No vaccine is currently available for human use, and treatment options remain costly and inaccessible for many at-risk populations.To achieve effective and sustainable control of zoonotic visceral leishmaniasis, critical gaps must be addressed through an integrated, One Health approach. This includes the development of DIVA-compatible vaccines and diagnostics, validation of immunological correlates of protection, standardized challenge models, and scalable intervention platforms. In parallel, efforts should focus on improving community engagement, strengthening surveillance, harmonizing movement control, and investing in operational research and delivery systems. Without coordinated action, leishmaniasis will continue to expand geographically and disproportionately affect the most vulnerable populations.

Sources of information

• Expert group composition

  Expert group members are included where permission has been given.

  Fabrizio Vitale, Istituto Zooprofilattico Sperimentale della Sicilia, Italy – [Leader]

  Gianluca Rugna, Istituto Zooprofilattico Sperimentale LER, Italy

  Lilia Zribi, Medical Parasitology, Biotechnology & Biomolecules, Istitut Pasteur de Tunis (extra EU)

  Karim Aoun, Professor Medical Parasitology, Biotechnology & Biomolecules, Istitut Pasteur de Tunis (extra EU)

  Liliana Colombo, MSD AH (Commercial)

  Carla Maia, Professor IHMT-NOVA, Portugal

  Sofia Boutsini, Head of department at veterinary Centre of Athens, Greece

• Date of submission by expert group

  29th July 2025

• References

  Recommended citation:

  "Vitale F.,Rugna G ., Zribi L.,Aoun K.,Colombo L., Maia C., Boutsini S., 2025. DISCONTOOLS chapter on Leishmaniasis https://www.discontools.eu/database/62-leishmaniasis.html.”

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• Name of reviewers

  Project Management Board.