Visceral Leishmaniasis (VL) Clinical Presentation, Laboratory Findings, Treatment Options and Outcome.

Background: Black disease, also known as visceral leishmaniasis (VL), is a parasitic illness caused by various Leishmania species. The risk of morbidity and mortality increases with delayed diagnosis and treatment. Early VL diagnosis and fast appropriate treatment are critical issues in endemic areas. Methods: This study was a retrospective cross-sectional study to investigate the diagnostic and therapeutic course of patients admitted with the diagnosis of VL in the Children's Medical Center (CMC) Hospital, Tehran, Iran. All cases of VL in patients under the age of 18 hospitalized between the years 2012 to 2022 were enrolled. Results: Twenty-seven patients were enrolled with an average age of 28.13 months with the majority of females (51.8%). Common clinical signs were fever (96.2%) and splenomegaly (92.59%). However, lymphadenopathy was rare. The largest number of patients was from Tehran Province, followed by Ardabil, Khuzestan, Gilan, and Alborz provinces. The most common hematological abnormalities were anemia (85.1%) and thrombocytopenia (44.4%). In accordance with the treatment strategy, liposomal amphotericin B and amphotericin B deoxycholate were given to 11 and 5 patients, respectively. Eleven of them received glucantime. The average length of hospitalization for liposomal amphotericin B was 15.36 ± 12.49 days. In comparison with glucantime (18.38 ±10.26 days) and amphotericin B deoxycholate (20.20± 6.18 days), liposomal amphotericin B group hospitalization was shorter than others were. Conclusion: VL should be included in the differential diagnosis of any child who presents with fever, splenomegaly, and anemia. Concerning the treatment strategy in this study, liposomal amphotericin B had more efficiency and shorter hospitalization duration.

Seroprevalence of visceral leishmaniasis among pregnant women in Jahrom city in Fars province, southern Iran.

Background: Visceral leishmaniasis (VL) is a public health issue in endemic countries with poor sanitation facilities. In this study, the seroprevalence rate and associated risk factors of VL were investigated during September 2020 to February 2021 in pregnant women referred to Ostad Mottahari and Peymanieh hospitals in Jahrom county, Fars province, southern Iran. Material and methods: A total of 220 serum samples of pregnant women were assessed for the presence of Anti-Leishmania infantum antibodies by direct agglutination antigen (DAT). The associated risk factors were obtained using questionnaires. Results: The overall seroprevalence of VL in pregnant women was 12.72% (28/220). Considering the antibody titer, titer 1:1600 was detected in 23 samples, titer 1:3200 in 4 samples, and titer 1:6400 in one sample. All 5 women with titer >3200 had mild fever. As such, there was a statistically significant difference regarding the age (≥39 years old with p-value: 0.01). Conclusions: We recommend an appropriate health education program for pregnant women and serological screening of VL before pregnancy in endemic cities. Moreover, we believed a need for more epidemiological studies for better understand the status of VL in pregnant women.

Spatio-Temporal Analysis and Clinical-Epidemiological Characterization of Visceral Leishmaniasis in Maranhão, Brazil, from 2009 to 2020.

This study was carried out to identify the spatial distribution and characterize the clinical-epidemiological profile of Visceral Leishmaniasis (VL) in Maranhão state, Brazil, from 2009 to 2020. This descriptive ecological study collected sociodemographic and clinical data of VL cases from the Brazilian Notifiable Diseases Information System database. A spatial autocorrelation analysis (Moran statistics) was performed. From 2009 to 2020, 5699 cases of VL were reported, with incidence of 6.5 cases/100,000 and prevalence of 7.1 cases/100,000. The temporal analysis showed a significant growth in incidence from 2009 to 2018, followed by a significant decrease between 2019 and 2020. The Moran map shows hotspots of high values in the central-west and central-east regions, and hotspots of low values in the northern region of Maranhão. The profile of patients affected by VL comprises males (OR = 1.8; IC95% = 1.72-1.92), aged under 14 years, brown, and with incomplete elementary schooling. The main symptoms reported were fever, fatigue, and edema. The main diagnostic method was laboratory. The mortality rate was 6.8%, and co-infection with HIV was reported by 8.5% of patients. The results of this study indicated the increase in incidence and lethality, as well as the expansion, of leishmaniasis in the state of Maranhão.

Privileged small molecules against neglected tropical diseases: A perspective from structure activity relationships.

Neglected tropical diseases (NTDs) comprise diverse infections with more incidence in tropical/sub-tropical areas. In spite of preventive and therapeutic achievements, NTDs are yet serious threats to the public health. Epidemiological reports of world health organization (WHO) indicate that more than 1.5 billion people are afflicted with at least one NTD type. Among NTDs, leishmaniasis, chagas disease (CD) and human African trypanosomiasis (HAT) result in substantial morbidity and death, particularly within impoverished countries. The statistical facts call for robust efforts to manage the NTDs. Currently, most of the anti-NTD drugs are engaged with drug resistance, lack of efficient vaccines, limited spectrum of pharmacological effect and adverse reactions. To circumvent the issue, numerous scientific efforts have been directed to the synthesis and pharmacological development of chemical compounds as anti-infectious agents. A survey of the anti-NTD agents reveals that the majority of them possess privileged nitrogen, sulfur and oxygen-based heterocyclic structures. In this review, recent achievements in anti-infective small molecules against parasitic NTDs are described, particularly from the SAR (Structure activity relationship) perspective. We also explore current advocating strategies to extend the scope of anti-NTD agents.

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.

Ulcerative Unilateral Tinea Manuum Caused by Nannizzia gypsea.

Dermatophytes, fungi specialized in keratin degradation, are key agents in skin infections, commonly referred to as tineas. Tinea manuum, affecting the hands, typically presents in noninflammatory or inflammatory forms, with ulcerative manifestations rarely reported. Nannizzia gypsea, a relatively uncommon cause of tineas, exhibits variable prevalence influenced by geographic factors. This study investigates a case of Ulcerative Unilateral Tinea Manuum caused by N. gypsea, aiming to explore the differential diagnosis, pathogenesis, and management. A 23-year-old female from the Yucatan Peninsula presented with an ulcerated lesion on her left hand. Initially suspected as Leishmaniasis, subsequent examination revealed tinea manuum. The study discusses differential diagnoses, highlighting the rarity of ulcerative presentations in dermatophytosis, and explores potential pathogenic mechanisms. This case underscores the importance of considering dermatophytes in ulcerative skin lesions and suggests a comprehensive diagnostic approach, particularly in endemic regions.

Laryngeal Leishmaniasis: A Neglected, Emerging Disease in Northern Italy.

Leishmaniasis represents an emerging public health issue in Mediterranean countries. The incidence of this condition has progressively risen in Northern Italy due to the growing number of immunocompromised people and probably due to climate changes. We hereby describe a case of relapsing laryngeal leishmaniasis in a female immunocompetent patient, presenting as aspecific chronic laryngitis. She was affected by severe asthma treated by inhaled steroid therapy, likely responsible for the parasite's diffusion through a locus minori resistentiae. The aspecific clinical presentation led to a delayed diagnosis and the lack of guidelines for the treatment caused multiple relapses. Biopsies of laryngeal lesions in the follow-up were performed by operative flexible videolaryngoscopy, thus avoiding general anesthesia and reducing associated healthcare costs. The aim of this report is to underline the diagnostic and therapeutic challenges that patients with this condition face and to present what is, to the best of our knowledge, the first application of prophylactic aerosolized pentamidine for relapsing laryngeal leishmaniasis.

Vitamin D-associated genetic variants in the Brazilian population: Investigating potential instruments for Mendelian randomization. / Variantes genéticas asociadas con la vitamina D en la población brasileña: investigación de potenciales instrumentos para aleatorización mendeliana

INTRODUCTION: Vitamin D is required for bone and mineral metabolism and participates in the regulation of the immune response. It is also linked to several chronic diseases and conditions, usually in populations of European descent. Brazil presents a high prevalence of vitamin D deficiency and insufficiency despite the widespread availability of sunlight in the country. Thus, it is important to investigate the role of vitamin D as a risk factor for disease and to establish causal relationships between vitamin D levels and health-related outcomes in the Brazilian population. OBJECTIVE: To examine genetic variants identified as determinants of serum vitamin D in genome-wide association studies of European populations and check whether the same associations are present in Brazil. If so, these single nucleotide polymorphisms (SNPs) could be developed locally as proxies to use in genetically informed causal inference methods, such as Mendelian randomization. MATERIALS AND METHODS: We extracted SNPs associated with vitamin D from the genomewide association studies catalog. We did a literature search to select papers ascertaining these variants and vitamin D concentrations in Brazil. RESULTS: GC was the gene with the strongest association with vitamin D levels, in agreement with existing findings in European populations. However, VDR was the most investigated gene, regardless of its non-existing association with vitamin D in the genomewide association studies. CONCLUSIONS: More research is needed to validate sound proxies for vitamin D levels in Brazil, for example, prioritizing GC rather than VDR.

Introducción. La vitamina D es necesaria para el metabolismo óseo y mineral, y participa en la regulación de la respuesta inmunitaria. También está relacionada con enfermedades crónicas en poblaciones europeas. En Brasil, existe una prevalencia elevada de deficiencia e insuficiencia de vitamina D, a pesar de la amplia disponibilidad de luz solar. Por lo tanto, es importante investigar el papel de la vitamina D como factor de riesgo de diversas enfermedades y establecer relaciones causales entre los niveles de vitamina D y los problemas de salud en la población brasileña. Objetivo. Examinar variantes genéticas relacionadas con la vitamina D sérica en estudios de asociación genómica de poblaciones europeas y comprobar si estas mismas están presentes en Brasil. De ser así, estos SNPs podrían utilizarse como proxies en métodos de inferencia causal, tales como la aleatorización mendeliana. Materiales y métodos. A partir del catálogo de estudios de asociación de genoma completo se extrajeron SNPs relacionados con los niveles de vitamina D. Luego se hizo una búsqueda bibliográfica para identificar los artículos que evaluaran estos SNPs y la concentración de vitamina D en Brasil. Resultados. GC fue el gen más fuertemente asociado con los niveles de vitamina D, en concordancia con los resultados existentes en poblaciones europeas. Sin embargo, el gen VDR fue el más investigado, aunque no esté vinculado con la vitamina D en los estudios de asociación de genoma completo. Conclusiones. Se necesita más investigación para validar proxies genéticos de los niveles de vitamina D en Brasil y se recomienda priorizar el gen GC en lugar de VDR.

Extracellular Vesicles: Translational Agenda Questions for Three Protozoan Parasites.

The protozoan parasites Plasmodium falciparum, Leishmania spp. and Trypanosoma cruzi continue to exert a significant toll on the disease landscape of the human population in sub-Saharan Africa and Latin America. Control measures have helped reduce the burden of their respective diseases-malaria, leishmaniasis and Chagas disease-in endemic regions. However, the need for new drugs, innovative vaccination strategies and molecular markers of disease severity and outcomes has emerged because of developing antimicrobial drug resistance, comparatively inadequate or absent vaccines, and a lack of trustworthy markers of morbid outcomes. Extracellular vesicles (EVs) have been widely reported to play a role in the biology and pathogenicity of P. falciparum, Leishmania spp. and T. cruzi ever since they were discovered. EVs are secreted by a yet to be fully understood mechanism in protozoans into the extracellular milieu and carry a cargo of diverse molecules that reflect the originator cell's metabolic state. Although our understanding of the biogenesis and function of EVs continues to deepen, the question of how EVs in P. falciparum, Leishmania spp. and T. cruzi can serve as targets for a translational agenda into clinical and public health interventions is yet to be fully explored. Here, as a consortium of protozoan researchers, we outline a plan for future researchers and pose three questions to direct an EV's translational agenda in P. falciparum, Leishmania spp. and T. cruzi. We opine that in the long term, executing this blueprint will help bridge the current unmet needs of these medically important protozoan diseases in sub-Saharan Africa and Latin America.

Alternative hosts of Leishmania infantum: a neglected parasite in Europe.

Multi-host pathogens that infect various animal species and humans are considered of great importance for public and animal health. Leishmania spp. parasites are a characteristic example of such pathogens. Although leishmaniosis in humans is endemic for about 100 countries around the world it is classified as a neglected tropical disease. There are three main forms of leishmaniosis in humans: cutaneous (CL), visceral (VL) and mucocutaneous leishmaniosis (MCL). Each year, about 30,000 new cases of VL and more than 1 million new cases of CL are recorded. In Europe L. infantum is the dominant species with dogs being reservoir hosts. Apart from dogs, infection has been recorded in various animals, which suggests that other species could play a role in the maintenance of the parasite in nature. Herein we provide an in-depth review of the literature with respect to studies that deal with Leishmania infantum infections in domestic and wild animal species in Europe. Given the fact that domesticated and wild animals could contribute to the incidences of leishmaniosis in humans, the aim of this paper is to provide a comprehensive review which could potentially be used for the development of measures when it comes to the control of the Leishmania infantum parasite.

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.

Demographic characteristics and prevalence of asymptomatic Leishmania donovani infection in migrant workers working in an endemic area in Northwest Ethiopia.

Introduction: Visceral leishmaniasis (VL), a neglected tropical disease that causes substantial morbidity and mortality, is a serious health problem in Ethiopia. Infections are caused by Leishmania (L.) donovani parasites. Most individuals remain asymptomatic, but some develop VL, which is generally fatal if not treated. We identified the area of Metema-Humera in Northwest Ethiopia as a setting in which we could follow migrant workers when they arrived in an endemic area. The demographic characteristics of this population and factors associated with their risk of asymptomatic infection are poorly characterised. Methods: We divided our cohort into individuals who visited this area for the first time (first comers, FC) and those who had already been in this area (repeat comers, RC). We followed them from the beginning (Time 1, T1) to the end of the agricultural season (Time 2, T2), performing tests for sand fly bite exposure (anti-sand fly saliva antibody ELISA) and serology for Leishmania infection (rK39 rapid diagnostic test and the direct agglutination test) at each time point and collecting information on risk factors for infection. Results: Our results show that most migrant workers come from non-endemic areas, are male, young (median age of 20 years) and are farmers or students. At T1, >80% of them had been already exposed to sand fly bites, as shown by the presence of anti-saliva antibodies. However, due to seasonality of sand flies there was no difference in exposure between FC and RC, or between T1 and T2. The serology data showed that at T1, but not at T2, a significantly higher proportion of RC were asymptomatic. Furthermore, 28.6% of FC became asymptomatic between T1 and T2. Over the duration of this study, one FC and one RC developed VL. In multivariable logistic regression of asymptomatic infection at T1, only age and the number of visits to Metema/Humera were significantly associated with asymptomatic infection. Conclusion: A better understanding of the dynamics of parasite transmission and the risk factors associated with the development of asymptomatic infections and potentially VL will be essential for the development of new strategies to prevent leishmaniasis.

Spatial analysis of American cutaneous leishmaniasis in the state of Amazonas.

OBJECTIVE: To evaluate, using spatial analysis, the occurrence of American Cutaneous Leishmaniasis (ACL) and analyze its association with the municipal human development index (MHDI) and deforestation in the state of Amazonas, Brazil, from 2016 to 2020. METHODS: This ecological study, carried out from January 2016 to December 2020, included the 62 municipalities of the state of Amazonas. The incidence rate of ACL was determined in space and time. Using Multiple Linear Regression by Ordinary Least Squares (OLS) and Spatial Autoregressive Regression (SAR) models, the relationship between incidence rates and Human Development Index (HDI) and deforestation was analyzed., The high- and low-risk clusters were identified by employing the Getis-Ord Gi* statistic. RESULTS: A total of 7,499 cases of ACL were registered in all 62 municipalities in the state. Most cases were in male (n=5,924; 79.24%), with the greatest frequency in the population aged from 20 to 39 years (n=3,356; 44.7%). The incidence rate in the state of Amazonas was 7.34 cases per 100,000 inhabitants-year, with the municipalities of Rio Preto da Eva and Presidente Figueiredo showing the highest rates (1,377.5 and 817.5 cases per 100,000 population-year, respectively). The ACL cases were clustered into specific areas related to those municipalities with the highest incidence rates. The SAR model revealed a positive relationship between ACL and deforestation. CONCLUSIONS: The occurrence of ACL was evident in a variety of patterns in the state of Amazonas; the high incidence rates and persistence of this disease in this state were linked to deforestation. The temporal distribution showed variations in the incidence rates during each year. Our results can help optimize the measures needed to prevent and control this disease in the state.

Geriatric cutaneous leishmaniasis: a retrospective analysis of 622 cases.

BACKGROUND: Cutaneous leishmaniasis (CL) is most common in childhood because children are exposed to the parasite early and, unlike adults, do not have immunity to CL. Since CL is less common in geriatric patients, clinical and epidemiological data in this age group are limited. This study aims to compare the clinical and demographic characteristics of geriatric patients diagnosed with CL with young patients. METHODS: In this retrospective study, 622 patients aged 65 and over and 6350 patients aged 19-64, who applied to Sanliurfa Oriental Boil Diagnosis and Treatment Center between January 2013 and February 2024 and were diagnosed with CL by parasitological examination, were included. Clinical and demographic characteristics of patients diagnosed with CL, such as age, gender, location of the lesion, lesion size, duration of the lesion, and treatments applied due to the diagnosis of CL, were recorded. Clinical and demographic characteristics of geriatric and young patients were compared. RESULTS: The mean age of elderly CL cases was 72.95 ± 6.54 years, and 65.2% were female. The most common clinical forms were ulcers (51.9%) and plaques (41%), respectively, in young and elderly patients. The most common locations of the lesions were upper limbs (54.8%) in all patients. The most preferred treatment method was intralesional (IL) meglumine antimoniate (MA) treatment (98.3%) in all patients. There were no difference between young and elderly CL cases in terms of mean number of lesions, average lesion duration, average lesion size, lesion location, clinical forms of lesions, and treatments options (P > 0.05). CONCLUSIONS: Based on the results of our study, it can be said that the clinical and demographic characteristics of CL are similar in young and old patients and systemic MA treatment shows similar clinical benefit in both age groups. In addition, it can be said that systemic MA therapy can be used safely in young patients and elderly patients without contraindications. IL MA therapy can be used in elderly patients where systemic MA therapy is contraindicated.

Distribution and Seasonal Variation of Phlebotomus and Sergentomyia Sand Fly Populations in Bhutan.

Leishmaniasis is considered one of the neglected tropical diseases in the world. Although Bhutan is a member of the visceral leishmaniasis elimination consortium in South Asia, not much attention has been accorded to the disease because of its low incidence. The vector that transmits Leishmania remains poorly understood. In this backdrop, sand-fly surveys were regularly conducted at multiple sites where leishmaniasis cases have been reported in Bhutan. Collections were made using CDC light traps and cattle-baited net traps in 15 villages from February 2019 to May 2022. Six species of Phlebotomus and four species of Sergentomyia were identified from these sites that included two Phlebotomus and three Sergentomyia species discovered for the first time in Bhutan. Sand-fly density varied significantly from village to village, and it showed strong seasonality with peak numbers collected from June to October and almost zero from December to February. Overall, sand-fly density was highest in the basements of the houses and were higher outdoors than indoors. Cattle-baited net traps collected few sand flies during the surveillance period. This work constituted the first systematic sand-fly population surveillance conducted in Bhutan and will provide a baseline for future vector ecology and Leishmania epidemiological studies.

Exploring the impact of epidemiological and clinical factors on the progression of canine leishmaniosis by statistical and whole genome analyses: from breed predisposition to comorbidities.

Canine leishmaniosis (CanL), caused by Leishmania infantum, is a complex disease of growing importance in Europe. Clinical manifestations result from the down-modulation of the host immune response through multiple host-parasite interactions. Although several factors might influence CanL progression, this is the first known study evaluating risk factors for its different clinical stages in a large referral hospital population (n = 35.669) from an endemic area, over a 20 year period. Genome-wide scans for selection signatures were also conducted to explore the genomic component of clinical susceptibility to L. infantum infection. The prevalence of CanL was 3.2% (16.7% stage I; 43.6% stage II; 32.1% stage III; 7.6% stage IV). Dog breed (crossbreed), bodyweight (<10 kg), living conditions (indoors), regular deworming treatment, and being vaccinated against Leishmania significantly decreased the transmission risk and the risk for developing severe clinical forms. Conversely, the detection of comorbidities was associated with advanced clinical forms, particularly chronic kidney disease, neoplasia, cryptorchidism, infectious tracheobronchitis and urate urolithiasis, although those did not impact the clinical outcome. Significant associations between an increased risk of severe clinical stages and findings in the anamnesis (renal or skin-related manifestations) and physical examination (ocular findings) were also detected, highlighting their diagnostic value in referred cases of CanL. Sixteen breeds were found to be significantly more susceptible to developing severe stages of leishmaniosis (e.g. Great Dane, Rottweiler, English Springer Spaniel, Boxer, American Staffordshire Terrier, Golden Retriever), while 20 breeds displayed a clinical resistantance phenotype and, thus, are more likely to mount an efficient immune response against L. infantum (e.g. Pointer, Samoyed, Spanish Mastiff, Spanish Greyhound, English Setter, Siberian Husky). Genomic analyses of these breeds retrieved 12 regions under selection, 63 candidate genes and pinpointed multiple biological pathways such as the IRE1 branch of the unfolded protein response, which could play a critical role in clinical susceptibility to L. infantum infection.

Leishmania Infection in Wild Lagomorphs and Domestic Dogs in North-East Spain.

Leishmania infantum is a zoonotic protozoan parasite distributed worldwide that is transmitted by phlebotomine sandflies. Dogs are the main reservoir for human infections. However, in recent years, the capacity of lagomorphs to contribute to Leishmania transmission has been confirmed. The present study aimed to assess Leishmania spp. exposure and infection in lagomorphs and sympatric domestic dogs in NE Spain. Sera from European hares, European rabbits, and rural dogs were tested for antibodies against L. infantum using an in-house indirect ELISA. PCR analysis targeting Leishmania spp. was performed in spleens from L. europaeus. Antibodies against Leishmania spp. were detected in all the species analyzed. Total sample prevalence was significantly higher in O. cuniculus (27.9%) than in L. europaeus (2.0%). Results of the PCR were all negative. The present study expands knowledge about Leishmania infections in free-ranging lagomorphs in the Iberian Peninsula, suggesting a more important role of O. cuniculus in the study area. Given the strong correlation between lagomorph densities and human leishmaniasis outbreaks in Spain, the high rabbit and human densities in NE Spain, and the high Leishmania spp. seroprevalence in rabbits, it becomes imperative to establish surveillance programs for lagomorphs in this region.

Using Passive Surveillance to Maintain Elimination as a Public Health Problem for Neglected Tropical Diseases: A Model-Based Exploration.

BACKGROUND: Great progress is being made toward the goal of elimination as a public health problem for neglected tropical diseases such as leprosy, human African trypanosomiasis, Buruli ulcer, and visceral leishmaniasis, which relies on intensified disease management and case finding. However, strategies for maintaining this goal are still under discussion. Passive surveillance is a core pillar of a long-term, sustainable surveillance program. METHODS: We use a generic model of disease transmission with slow epidemic growth rates and cases detected through severe symptoms and passive detection to evaluate under what circumstances passive detection alone can keep transmission under control. RESULTS: Reducing the period of infectiousness due to decreasing time to treatment has a small effect on reducing transmission. Therefore, to prevent resurgence, passive surveillance needs to be very efficient. For some diseases, the treatment time and level of passive detection needed to prevent resurgence is unlikely to be obtainable. CONCLUSIONS: The success of a passive surveillance program crucially depends on what proportion of cases are detected, how much of their infectious period is reduced, and the underlying reproduction number of the disease. Modeling suggests that relying on passive detection alone is unlikely to be enough to maintain elimination goals.

The Hidden Hand of Asymptomatic Infection Hinders Control of Neglected Tropical Diseases: A Modeling Analysis.

BACKGROUND: Neglected tropical diseases are responsible for considerable morbidity and mortality in low-income populations. International efforts have reduced their global burden, but transmission is persistent and case-finding-based interventions rarely target asymptomatic individuals. METHODS: We develop a generic mathematical modeling framework for analyzing the dynamics of visceral leishmaniasis in the Indian sub-continent (VL), gambiense sleeping sickness (gHAT), and Chagas disease and use it to assess the possible contribution of asymptomatics who later develop disease (pre-symptomatics) and those who do not (non-symptomatics) to the maintenance of infection. Plausible interventions, including active screening, vector control, and reduced time to detection, are simulated for the three diseases. RESULTS: We found that the high asymptomatic contribution to transmission for Chagas and gHAT and the apparently high basic reproductive number of VL may undermine long-term control. However, the ability to treat some asymptomatics for Chagas and gHAT should make them more controllable, albeit over relatively long time periods due to the slow dynamics of these diseases. For VL, the toxicity of available therapeutics means the asymptomatic population cannot currently be treated, but combining treatment of symptomatics and vector control could yield a quick reduction in transmission. CONCLUSIONS: Despite the uncertainty in natural history, it appears there is already a relatively good toolbox of interventions to eliminate gHAT, and it is likely that Chagas will need improvements to diagnostics and their use to better target pre-symptomatics. The situation for VL is less clear, and model predictions could be improved by additional empirical data. However, interventions may have to improve to successfully eliminate this disease.

Genetic diversity in Leishmania infantum and Leishmania tropica isolates from human and canine hosts in northern Morocco.

This study investigated nine provinces in northern Morocco and collected 275 skin scraping, 22 bone marrow aspirates, and 89 fine needle aspirations from suspected cutaneous leishmaniasis (CL) and visceral leishmaniasis (VL) patients and potentially infected dogs. Molecular analysis using ITS1 RFLP PCR and RT-PCR revealed a higher prevalence of L. infantum (66.18 %; χ2 = 28.804; df = 1; P-value = 8.01e-08) than L. tropica in skin scraping, with L. infantum being the sole causative agent for both VL and canine leishmaniasis. L. infantum was predominantly found in most provinces, while L. tropica was relatively more dominant in Taza Province. Discriminant Analysis of Principal Components (DAPC) revealed distinct clustering between L. tropica and the other three species. However, no small subset of SNPs could clearly differentiate between Infantum_CL, Infantum_VL, and CanL, as they likely share a significant genetic background. The high rate of L. infantum could be attributed to the abundance of sand fly species transmitting VL. In Taza Province, Phlebotomus sergenti, responsible for anthroponotic CL, is the most abundant species. DNA sequencing demonstrated sequence heterogeneity in L. infantum (variants 1 to 9) and L. tropica (variants 1 to 7). Phylogenetic analysis showed a distinct separation between L. tropica and L. infantum strains, with an overlap among L. infantum strains isolated from cutaneous, visceral, and canine cases, and dogs serving as the central population for L. infantum.