Sex-structured disease transmission model and control mechanisms for visceral leishmaniasis (VL).

BACKGROUND: Leishmaniasis are a group of diseases caused by more than 20 species of the protozoan that are transmitted through the bite of female sand fly. The disease is endemic to 98 countries of the world. It affects most commonly the poorest of the poor and mainly males. Several research has been conducted to propose disease control strategies. Effective medical care, vector control, environmental hygiene, and personal protection are the mainstays of the current preventative and control methods. The mathematical models for the transmission dynamics of the disease studied so far did not consider the sex-biased burden of the disease into consideration. METHODOLOGY: Unlike the previous VL works, this study introduces a new deterministic sex-structured model for understanding the transmission dynamics of visceral leishmaniasis. Basic properties of the model including basic reproduction number ([Formula: see text]), and conditions for the existence of backward bifurcation of the model are explored. Baseline parameter values were estimated after the model was fitted to Ethiopia's VL data. Sensitivity analysis of the model was performed to identify the parameters that significantly impact the disease threshold. Numerical simulations were performed using baseline parameter values, and scenario analysis is performed by changing some of these parameters as appropriate. CONCLUSION: The analysis of the model shows that there is a possibility for a backward bifurcation for [Formula: see text], which means bringing [Formula: see text] to less than unity may not be enough to eradicate the disease. Our numerical result shows that the implementation of disease-preventive strategies, as well as effectively treating the affected ones can significantly reduce the disease prevalence if applied for more proportion of the male population. Furthermore, the implementation of vector management strategies also can considerably reduce the total prevalence of the disease. However, it is demonstrated that putting more effort in treating affected reservoir animals may not have any significant effect on the overall prevalence of the disease as compared to other possible mechanisms. The numerical simulation infers that a maximum of 60% of extra preventative measures targeted to only male population considerably reduces the total prevalence of VL by 80%. It is also possible to decrease the total prevalence of VL by 69.51% when up to 50% additional infected males receive treatment with full efficacy. Moreover, applying a maximum of 15% additional effort to reduce the number of vectors, decreases the total VL prevalence by 57.71%. Therefore, in order to reduce the disease burden of visceral leishmaniasis, public health officials and concerned stakeholders need to give more emphasis to the proportion of male humans in their intervention strategies.

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

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

Phlebotomine sand fly (Diptera: Phlebotominae) diversity in the foci of cutaneous leishmaniasis in the Surxondaryo Region of Uzbekistan: 50 years on.

In Uzbekistan, the number of reported leishmaniasis cases is rising at the alarming rate. In this work, we studied the phlebotomine sand fly (Diptera: Phlebotominae) diversity in the foci of cutaneous leishmaniasis in the Surxondaryo Region of Uzbekistan and compared it with the data obtained for the same area 50 years ago, when infection prevalence was reportedly low. We found that the implicated vector for zoonotic leishmaniasis, P. papatasi, remained eudominant; the proportion of implicated anthroponotic leishmaniasis vector, P. sergenti, rose significantly from averaged 5.4 to 41.4%; Phlebotomus alexandri, a suspected visceral leishmaniasis vector, was eudominant at two sites, and a second suspected vector for this disease, P. longiductus, was newly recorded in the region. We conclude that the increase in the documented cases of cutaneous leishmaniasis in the Surxondaryo Region of Uzbekistan may be connected to the changes in fauna of sand flies vectoring Leishmania spp.

Efforts toward the Elimination of Visceral Leishmaniasis in South Asia: A Review of Progress in Bhutan.

Leishmaniases are a group of diseases under the category of neglected tropical diseases targeted for global elimination. However, they continue to pose major clinical and public health problems, especially among those living in poor socioeconomic conditions. Here, we summarize leishmaniasis elimination efforts in Bhutan. Between 1994 and 2022, Bhutan recorded 54 cases of leishmaniasis across 14 of its 20 districts. There are seven species of Phlebotomus and three species of Sergentomyia sand flies documented in the country. At a subnational level, all endemic districts recorded a visceral leishmaniasis annual incidence <1 per 10,000 population, meeting the regional elimination targets. Serological testing with ELISA and molecular testing with polymerase chain reaction were established at the Royal Center for Disease Control in 2022. A leishmaniasis prevention and management guideline was adopted in 2023 to aid clinicians in diagnosis and management. Active and passive case surveillance was integrated with the national infectious disease early warning and response system. Risk-based entomological surveillance and control have also been prioritized. Climate change may play a major role in rendering districts in the temperate zone favorable for vector proliferation. The country's medical university introduced a diploma course in medical entomology in 2023 to augment the human resources needed for vector surveillance efforts. However, leishmaniasis elimination lacks dedicated programmatic management amid competing priorities for resources against other infectious diseases. Leishmaniasis elimination requires a targeted and programmatic approach in Bhutan, including cross-border collaborative efforts with neighboring Indian states. Bhutan remains highly committed to achieving leishmaniasis elimination targets.

The spleen is the graveyard of CD4+ cells in patients with immunological failure of visceral leishmaniasis and AIDS.

BACKGROUND: Visceral leishmaniasis (VL), or kala-azar, is a common comorbidity in patients with AIDS in endemic areas. Many patients continue to experiences relapses of VL despite virological control, but with immunological failure. These patients remain chronically symptomatic with hypersplenism, for example with anemia, leukopenia, and thrombocytopenia, and are at risk of severe co-infection due to low CD4+ count. Therefore, in this study, splenectomized patients with VL and HIV infection were investigated to understand why the CD4+ count fails to recover in these patients, evaluating the importance of spleen mass for hypersplenism and immunological failure. METHODS: From a retrospective open cohort of 13 patients who had previously undergone splenectomy as salvage therapy for relapsing VL, 11 patients with HIV infection were investigated. This study compared the patients' complete blood cell count (CBC) and CD4+ and CD8+ cell counts before and after splenectomy with respect to spleen weight. RESULTS: CBC was substantially improved after splenectomy, indicating hypersplenism. However, to the best of our knowledge, this is the first study to show that spleen mass is strongly and negatively correlated with CD4+ cell count (ρ = -0.71, P = 0.015). CONCLUSIONS: This finding was unexpected, as the spleen is the most extensive lymphoid tissue and T-lymphocyte source. After reviewing the literature and reasoning, we hypothesized that the immunological failure was secondary to CD4+ loss initially by apoptosis in the spleen induced by productive HIV infection and, subsequently, by pyroptosis sustained by parasitic infection in spleen macrophages.

Detection and phylogenetic analysis of kinetoplast DNA of Leishmania infantum infected humans, domestic dogs and sandflies in Northwest Iran.

Leishmaniasis refers to a disease with a wide range of manifestations; and there are three main forms of disease, cutaneous, mucocutaneous, and visceral. Leishmaniasis is one of the diseases with a protozoan agent which is vector-borne. Visceral leishmaniasis (VL) is the most severe form that can be fiercely life-threatening if left untreated. VL can be caused by members of Leishmania donovani complex, in Iran, Leishmania infantum is considered the primary causative agent of VL, resulting in a zoonotic form of VL. The two main goals of our work, which followed our prior sero-epidemiological and entomological survey, were to characterize and conduct a phylogenetic analysis of the Leishmania species that infect people, dogs, and sandflies. The samples were collected throughout 2017, from January to December, so blood samples were collected from humans and dogs, while sandfly samples were collected with sticky traps. DNA extracted from all seropositive samples of humans and dogs, 10% of sero-negative human samples, and all collected sandflies were subjected to kDNA-nested-PCR for tracing parasites. A total of 30 samples, including 20 human samples, 8 dog samples, and 2 sandfly samples, were found positive for the kDNA gene of L. infantum. Sequences were evaluated to study the genetic diversity among the six discovered L. infantum. Based on kDNA, the phylogenetic study of L. infantum demonstrated a high level of genetic variety and a relationship between the host, the parasite's geographic origin, and its genetic diversity.

Challenges for maintaining post elimination phase of visceral leishmaniasis control programme in India: A field-based study.

BACKGROUND: India is going through the maintenance phase of VL elimination programme which may be threatened by the persistence of hidden parasite pools among asymptomatic leishmanial infection (ALI) and PKDL. The present work was designed to determine the burden of VL, PKDL, and ALI and to assess the role of treatment of ALI in maintaining post-elimination phase. METHODS AND FINDING: The study was undertaken in Malda district, West Bengal, India during October 2016 to September 2021. Study areas were divided into 'Study' and 'Control' arms. VL and PKDL cases of both the arms were diagnosed by three active mass surveys with an interval of one year and treated as per National guideline. ALI of 'Study' arm was treated like VL. ALI of 'Control' arm was followed up to determine their fate. Fed sand-fly pools were analysed for parasitic DNA. No significant difference was noted between the incidence of VL and PKDL in both the arms. Incidence of ALI declined sharply in 'Study' arm but an increasing trend was observed in 'Control' arm. Significantly higher rate of sero-conversion was noted in 'Control' arm and was found to be associated with untreated ALI burden. Parasitic DNA was detected in 22.8% ALI cases and 2.2% sand-fly pools. CONCLUSION: Persistence of a significant number of PKDL and ALI and ongoing transmission, as evidenced by new infection and detection of leishmanial DNA in vector sand-flies, may threaten the maintenance of post-elimination phase. Emphasis should be given for elimination of pathogen to prevent resurgence of VL epidemics.

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

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

[Current prevalence and control strategies of visceral leishmaniasis in Sichuan Province: A review].

Visceral leishmaniasis is a parasitic disease transmitted by Phlebotomus chinensis that poses a great threat to human health. Historically, visceral leishmaniasis was predominantly prevalent in northwestern regions of Sichuan Province. Following the founding of the People's Republic of China, large-scale integrated interventions had been implemented in visceral leishmaniasis-endemic areas of Sichuan Province, including identification and treatment of visceral leishmaniasis patients, elimination of infected dogs, Ph. chinensis control and health education. This review summarizes the prevalence of visceral leishmaniasis, discusses the control strategy of visceral leishmaniasis and analyzes the challenges of elimination of visceral leishmaniasis based on the One Health concept in Sichuan Province, so as to provide insights into elimination of visceral leishmaniasis in the province.

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

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

In vitro growth of Leishmania parasites from biopsy samples of suspected cutaneous and visceral leishmaniasis cases in Sri Lanka: An observational study.

Sri Lanka reports a large focus of Leishmania donovani caused cutaneous leishmaniasis (CL). Subsequent emergence of visceral leishmaniasis (VL) was also reported recently. Expansion of the on-going disease outbreak and many complexities indicate urgent need to enhance early case detection methods. In vitro cultivation (IVC) of parasites causing visceral leishmaniasis (VL) is important for disease confirmation and to obtain sufficient quantities of parasites required in many scientific studies. IVC is carried out as a useful second line investigation for direct microscopy negative patients with CL in this setting. Along with the emergence of VL, current study was carried out to evaluate in vitro growth of local VL parasites and to identify their differences associated with in vitro growth characteristics. Routine parasitological diagnostic methods, i.e., light microscopy (LM), polymerase chain reaction (PCR) were used for confirmation of suspected cases. Lesion samples from 125 suspected CL cases and bone marrow or splenic aspirations from 125 suspected VL patients were used to inoculate IVCs. Media M199 (about 70 µl) supplemented with 15-20% of heat inactivated fetal bovine serum was used for initial culturing procedures in capillaries. Capillary cultures were monitored daily. Total of 44 different compositions/conditions were used for evaluating in vitro growth of VL causing parasite. Daily records on parasite counts, morphological appearance (size, shape, and wriggly movements) were maintained. In vitro transformation of Leishmania promastigotes to amastigotes and outcome of the attempts on recovery of live Leishmania from culture stabilates was also compared between CL and VL parasites. Proportion of cultures showing a transformation of promastigotes were 40/45 (88.9%) and 4/10 (40.0%) for CL and VL respectively. In the transformed cultures, parasites showing typical shape, size and movement patterns were less in VL (1/4, 25.0%) compared to CL (28/40, 70.0%). CL cultures showed a growth up to mass culturing level with mean duration of two weeks while it was about five weeks for VL cultures. Proportion of cultures that reached a parasite density of 1 × 106 cells/ml (proceeded to mass cultures) was significantly low in VL (4/10, 40%) as compared to CL (28/40, 70.0%). None of media compositions/conditions were successful for mass culturing of VL parasites while all of them were shown to be useful for growing CL strains. Also in vitro transformation to amastigote form and recovering of culture stabilates were not successful compared to CL. There were clear differences between in vitro growth of Leishmania parasites causing local CL and VL. Further studies are recommended for optimization of in vitro culturing of VL parasite which will be invaluable to enhance case detection in future.

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

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

Characterisation of an area of coexistent visceral and cutaneous leishmaniasis transmission in the State of Piauí, Brazil.

BACKGROUND: In Brazil, transmission of visceral and cutaneous leishmaniasis has expanded geographically over the last decades, with both clinical forms occurring simultaneously in the same area. OBJECTIVES: This study characterised the clinical, spatial, and temporal distribution, and performed entomological surveillance and natural infection analysis of a leishmaniasis-endemic area. METHODS: In order to characterise the risk of leishmaniasis transmission in Altos, Piauí, we described the clinical and socio-demographic variables and the spatial and temporal distribution of cases of American visceral leishmaniasis (AVL) and American cutaneous leishmaniasis (ACL) cases and identified potential phlebotomine vectors. FINDINGS: The urban area concentrated almost 54% of ACL and 86.8% of AVL cases. The temporal and spatial distribution of AVL and ACL cases in Altos show a reduction in the number of risk areas, but the presence of permanent disease transmission foci is observed especially in the urban area. 3,808 phlebotomine specimens were captured, with Lutzomyia longipalpis as the most frequent species (98.45%). Of the 35 females assessed for natural infection, one specimen of Lu. longipalpis tested positive for the presence of Leishmania infantum and Leishmania braziliensis DNA. MAIN CONCLUSION: Our results indicate the presence of risk areas for ACL and AVL in the municipality of Altos and highlight the importance of entomological surveillance to further understand a possible role of Lu. longipalpis in ACL transmission.

Source Tracing of Leishmania donovani in Emerging Foci of Visceral Leishmaniasis, Western Nepal.

We sequenced Leishmania donovani genomes in blood samples collected in emerging foci of visceral leishmaniasis in western Nepal. We detected lineages very different from the preelimination main parasite population, including a new lineage and a rare one previously reported in eastern Nepal. Our findings underscore the need for genomic surveillance.

Spatial analysis of the risk for canine visceral leishmaniasis in an urban area in the State of Sergipe.

Visceral Leishmaniasis is included among the neglected tropical diseases, being directly related to conditions of social vulnerability, in urban environments, dogs act as important reservoirs. The aim of the study was to evaluate the distribution of dogs, related risk factors and identify of volatile organic compounds from infected dogs. Peripheral blood samples from 72 dogs were collected for detection using the ELISA test, in addition to hair samples for analysis by GC-MS. Of the evaluated dogs, 13 (18.05%/72) were reactive for canine VL, seven in Aracaju and six in Propriá. Factors related to vegetation, age, place where the dog stays and free access to the street, were associated with a greater chance of the dog becoming infected. Fifty-three compounds were identified from ten canine hair samples, among which 2-butoxyethanol, benzaldehyde, decane, 2-phenylacetaldehyde, nonan-1-ol, 2-phenoxyethanol, nonanoic acid, 8-heptadecene and eicosane were found in seropositive dogs for leishmaniasis. The guardian's posture has been increasingly important, requiring more attention to the dog's health and actions aimed at environmental management in an attempt to reduce cases of canine VL in the state. Even though the identified VOCs have not been associated with leishmanial infection, it is of great use for understanding canine hair substances.

Epidemiology of visceral leishmaniasis in municipalities of Mato Grosso and the performance of surveillance activities: an updated investigation.

Visceral leishmaniasis (VL) is considered a globally neglected disease. To address the problem of VL endemic to Brazil, the Visceral Leishmaniasis Control Program (VLCP) was created, which recommends the development of health surveillance actions such as the identification of human and canine cases, vector control and prevention of disease. We aimed to investigate the epidemiological situation of VL in municipalities of the State of Mato Grosso (MT) and assess the execution of VLCP activities. Data on human cases were obtained from the Information System for Notifiable Diseases (SINAN), and data from entomological and canine inquiry were provided by the State's Health Department. Analyzes from the period 2019 - 2021 recorded 30 cases of human VL, distributed among 16 municipalities. Vectors were identified in 50% of the municipalities where entomological investigations were carried out, and the predominant specie was Lutzomyia longipalpis. A total of 15,585 dogs were subjected to serological examination, of which 18.91% tested seropositive for Leishmania infantum. However, it must be emphasized that only three municipalities conducted consecutive inquiries involving canine VL. Although VL is distributed widely throughout the State, only a few municipalities have undertaken the actions of the VLCP, thus highlighting the neglected status of the disease.

Re-emergence of human leishmaniasis in northern Italy, 2004 to 2022: a retrospective analysis.

BackgroundHuman leishmaniasis is a protozoan disease transmitted by sand flies and endemic in the Mediterranean region. In Italy, leishmaniasis is present in the south and the western coastal regions, with an epidemic peak detected in northern Italy in the early 1970s.AimTo examine temporal trends, and demographic, clinical, geographical and environmental features of human leishmaniasis cases recorded by the local health unit (LHU) of Bologna, northern Italy.MethodsIn this retrospective observational study, we analysed human leishmaniasis cases recorded from 2004 to 2022 within the Bologna LHU. We also conducted serological investigations for canine leishmaniasis in owned dogs living near the place of infection of human cases.ResultsIn total, 173 cases of human leishmaniasis were detected, and 154 cases were considered autochthonous. An increase of human cases was observed since 2004, with incidence peaks above 2 cases/100,000 inhabitants in 2013, 2018 and 2022; epidemic peaks were preceded by dry summers. Most cases lived in the plain and hilly areas less than 400 m above sea level and many resided in isolated housing, in city outskirts, and/or near uncultivated areas, watercourses and railway sections. The incidence of canine leishmaniasis did not increase in the study period.ConclusionAn epidemic of human leishmaniasis with fluctuating annual numbers of cases, probably related to environmental and climatic factors, was identified in the Bologna LHU. Understanding the risk factors and the environmental characteristics related to places of infection is crucial to evaluate the public health implications of leishmaniasis.

Association between living in the endemic area and level of knowledge of visceral leishmaniasis.

BACKGROUND: Iran is a country with a high prevalence of visceral leishmaniasis (VL) and seven endemic provinces. In this study, we tried to identify unobserved classes of knowledge among Iranians toward VL and assess the predictors of each latent class. METHODS: This cross-sectional study was conducted among randomly selected participants from endemic and non-endemic areas of VL in Iran in 2020 and 2021. The collected data included demographic characteristics and questions about knowledge, attitude, and practice toward VL. We performed latent class analysis using a procedure for latent class analysis (PROC LCA) in SAS to identify the class membership of knowledge of participants toward VL. RESULTS: Five latent classes were identified: very low (38.9%), low (15.5%), moderate (6.2%), high (14.1%), and very high (25.2%) knowledge about VL. Living in endemic areas significantly increased the odds of belonging to the low (adjusted OR (AOR = 7.23; 95% confidence interval (CI):4.52-11.58), high (AOR = 2.71; 95%CI: 1.73-4.23), and very high (AOR = 8.47; 95%CI: 5.78-12.41) classes compared to the very low class. Also, having academic education increased the odds of membership in the very high class (AOR = 2.36; 95%CI: 1.61-3.47) compared to the very low class. CONCLUSION: This study revealed that more than 50% of the participants fell into the latent classes of very low and low knowledge toward VL. Some educational workshops in the endemic areas could be effective in enhancing knowledge about VL.

Comparative genomics of Leishmania donovani progeny from genetic crosses in two sand fly species and impact on the diversity of diagnostic and vaccine candidates.

Sand fly transmitted Leishmania species are responsible for severe, wide ranging, visceral and cutaneous leishmaniases. Genetic exchange can occur among natural Leishmania populations and hybrids can now be produced experimentally, with limitations. Feeding Phlebotomus orientalis or Phlebotomus argentipes on two strains of Leishmania donovani yielded hybrid progeny, selected using double drug resistance and fluorescence markers. Fluorescence activated cell sorting of cultured clones derived from these hybrids indicated diploid progeny. Multilocus sequence typing of the clones showed hybridisation and nuclear heterozygosity, although with inheritance of single haplotypes in a kinetoplastid target. Comparative genomics showed diversity of clonal progeny between single chromosomes, and extraordinary heterozygosity across all 36 chromosomes. Diversity between progeny was seen for the HASPB antigen, which has been noted previously as having implications for design of a therapeutic vaccine. Genomic diversity seen among Leishmania strains and hybrid progeny is of great importance in understanding the epidemiology and control of leishmaniasis. As an outcome of this study we strongly recommend that wider biological archives of different Leishmania species from endemic regions should be established and made available for comparative genomics. However, in parallel, performance of genetic crosses and genomic comparisons should give fundamental insight into the specificity, diversity and limitations of candidate diagnostics, vaccines and drugs, for targeted control of leishmaniasis.

Effect of environmental variables on the incidence of Visceral Leishmaniasis in Brazil and Colombia.

Visceral Leishmaniasis (VL) is the most severe of the three forms of Leishmaniasis. In the Americas, Brazil and Colombia present more than 90 % of the cases in the region. Our aim in this research was to estimate the association of the incidence rate of Visceral Leishmaniasis with the following environmental variables: the percentage of area suitable for the vector Lutzomyia longipalpis, the episodes of La Niña and El Niño, the Brazilian and Colombian biomes. Epidemiological data were obtained from the Brazilian Notifiable Diseases Information System and the Colombian National Public Health Surveillance System. Environmental data were downloaded from the NASA Giovanni web app, the Modis Sensor database, and the meteorological agencies of Australia, Japan, and the United States of America. Records of the presence of Lu. longipalpis were obtained from public databases and previous studies. As a result, the incidence per 10,000 inhabitants with LEBS for each El Niño-Southern Oscillation (ENSO) episode showed the largest values during El Niño 2015-2016, mainly in Brazil's Northeast and Central regions and the Northeast region of Colombia. Compared with the Neutral 2012-2014 episode, the episodes of El Niño 2015-2016 and La Niña 2010-2011 showed an average increase in the monthly incidence rate of VL, and the average increase was higher during El Niño 2015-2016 (aIRR = 2.304 vs.1.453) We found a positive association between the incidence rate of VL and the El Niño 2015-2016 episode and an impressive% of area suitable for the vector Lu. longipalpis in the Amazon region.An increase of 1 % in the area suitable for the vector Lu. longipalpis leads to an average rise of 0.8 % in the monthly incidence rate of VL. Our study shows a possible association between VL incidence and ENSO, with the most considerable incidence rates observed during El Niño 2015-2016 in Brazil's Northeast and Central regions and the Northeast region of Colombia. The present study is very important to better understand the Visceral Leishmaniasis transmission dynamics.