Increasing incidence of zoonotic visceral leishmaniasis on Crete, Greece.
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ABSTRACT:
SUBMITTER: Antoniou M
PROVIDER: S-EPMC2727332 | biostudies-literature | 2009 Jun
REPOSITORIES: biostudies-literature
Publications
Increasing incidence of zoonotic visceral leishmaniasis on Crete, Greece.
Antoniou Maria M Messaritakis Ippokratis I Christodoulou Vasiliki V Ascoksilaki Ioanna I Kanavakis Nikos N Sutton Andrew J AJ Carson Connor C Courtenay Orin O
Emerging infectious diseases 20090601 6
To determine whether the incidence of canine leishmaniasis has increased on Crete, Greece, we fitted infection models to serodiagnostic records of 8,848 dog samples for 1990-2006. Models predicted that seroprevalence has increased 2.4% (95% confidence interval 1.61%-3.51%) per year and that incidence has increased 2.2- to 3.8-fold over this 17-year period. ...[more]
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Project description:BackgroundZoonotic visceral leishmaniasis (ZVL) caused by Leishmania infantum is endemic with an epidemiological profile of a paediatric disease in Tunisia. In the context of a high fatality rate, identifying risk factors for in-hospital mortality in children treated for ZVL is of major epidemiological importance.DesignA retrospective (case-control) study included 230 immuno-competent children diagnosed and confirmed with primary ZVL in the paediatric department of the University Hospital of Kairouan between 2004 and 2014. Forty-seven per cent (47%) were children under 18 months of age, and with a male ⁄ female ratio of 1.01:1.ResultsThe overall case-fatality was 6% (n = 14). The risk factors for in-hospital death identified by a multivariate analysis were: bleeding at admission (OR = 25.5, 95% CI: 2.26-287.4; p = 0.009), white cell count less than 4000/mm3 (OR = 5.66, 95% CI: 1.16-27.6; p = 0.032), cytolysis (OR = 28.13, 95% CI: 4.55-173.6; p < 0.001), and delay between onset of symptoms and admission ≥ 15 days (OR = 11, 95% CI: 1.68-72; p = 0.012).ConclusionThe results strongly suggest that paediatric patients admitted 15 days after onset of symptoms, with bleeding, white cell counts below 4,000/mm3, and cytolysis at admission should be considered severe cases and subsequently, they are at high risk of mortality. A better understanding of factors associated with death of children from ZVL may contribute to decrease mortality.
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Project description:BackgroundVisceral Leishmaniasis (VL) is endemic in South Sudan, manifesting periodically in major outbreaks. Provision of treatment during endemic periods and as an emergency response is impeded by instability and conflict. Médecins Sans Frontières (MSF) has provided health care in South Sudan since the late 1980's, including treatment for 67,000 VL patients. In recent years, MSF monitoring data have indicated increasing numbers of VL relapse cases. A retrospective analysis of these data was performed in order to provide insight into the possible causes of this increase.Methodology/principal findingsProgramme monitoring data from the MSF hospital in Lankien, Jonglei State, South Sudan, for the period 2001-2018 were analysed to detect trends in VL relapse as a proportion of all VL cases presenting to MSF treatment centres. Routinely collected patient-level data from relapse and primary VL cases treated at all MSF sites in South Sudan over the same period were analysed to describe patient characteristics and treatments received. VL relapse as a proportion of all VL cases increased by 6.5% per annum (95% CI 0.3% to 13.0%, p = 0.04), from 5.2% during 2001-2003 to 14.4% during 2016-2018. Primary VL and VL relapse patients had similar age, sex and anthropometric characteristics, the latter indicating high indices of undernutrition which were relatively constant over time. Clinical factors (Hb, spleen size, and VL severity score) also did not vary substantially over time. SSG/PM was the main treatment regimen from 2001-2018, used in 68.7% of primary and 70.9% of relapse VL cases; AmBisome was introduced in 2013, received by 22.5% of primary VL and 32.6% of VL relapse cases from 2013-2018.ConclusionIncreasing incidence of VL relapse in South Sudan does not appear to be explained by changes in patient characteristics or other factors. Our data are concerning and may indicate an emergence of treatment-resistant parasite strains, decreasing the effectiveness of treatment regimens. This warrants further investigation as a causal factor. New chemical entities that will enable safe and highly effective short-course oral treatments for VL are urgently needed.
| S-EPMC9426874 | biostudies-literature
Project description:Human visceral leishmaniasis (VL) vaccines are currently under development and there is a need to understand their potential impact on population wide VL incidence. We implement four characteristics from different human VL vaccine candidates into two published VL transmission model variants to estimate the potential impact of these vaccine characteristics on population-wide anthroponotic VL incidence on the Indian subcontinent (ISC). The vaccines that are simulated in this study 1) reduce the infectiousness of infected individuals towards sand flies, 2) reduce risk of developing symptoms after infection, 3) reduce the risk of developing post-kala-azar dermal leishmaniasis (PKDL), or 4) lead to the development of transient immunity. We also compare and combine a vaccine strategy with current interventions to identify their potential role in elimination of VL as a public health problem. We show that the first two simulated vaccine characteristics can greatly reduce VL incidence. For these vaccines, an approximate 60% vaccine efficacy would lead to achieving the ISC elimination target (<1 VL case per 10,000 population per year) within 10 years' time in a moderately endemic setting when vaccinating 100% of the population. Vaccinating VL cases to prevent the development of PKDL is a promising tool to sustain the low incidence elimination target after regular interventions are halted. Vaccines triggering the development of transient immunity protecting against infection lead to the biggest reduction in VL incidence, but booster doses are required to achieve perduring impact. Even though vaccines are not yet available for implementation, their development should be pursued as their potential impact on transmission can be substantial, both in decreasing incidence at the population level as well as in sustaining the ISC elimination target when other interventions are halted.
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Project description:With several decades of concerted control efforts, visceral leishmaniasis(VL) eradication had almost been achieved in China. However, VL cases continue to be detected in parts of western China recent years. Using data of reported cases, this study aimed to investigate the epidemiology and spatio⁃temporal distribution, of mountain-type zoonotic visceral leishmaniasis (MT-ZVL) in China between the years 2015 and 2019. Epidemiological data pertaining to patients with visceral leishmaniasis (VL) were collected in Gansu, Shaanxi, Sichuan, Shanxi, Henan and Hebei provinces between the years 2015 and 2019. Joinpoint regression analysis was performed to determine changes in the epidemic trend of MT-ZVL within the time period during which data was collected. Spatial autocorrelation of infection was examined using the Global Moran's I statistic wand hotspot analysis was carried out using the Getis-Ord Gi* statistic. Spatio-temporal clustering analysis was conducted using the retrospective space-time permutation flexible spatial scanning statistics. A total of 529 cases of MT-ZVL were detected in the six provinces from which data were collected during the study time period, predominantly in Gansu (55.0%), Shanxi (21.7%), Shaanxi (12.5%) and Sichuan (8.9%) provinces. A decline in VL incidence in China was observed during the study period, whereas an increase in MT-ZVL incidence was observed in the six provinces from which data was obtained (t = 4.87, P < 0.05), with highest incidence in Shanxi province (t = 16.91, P < 0.05). Significant differences in the Moran's I statistic were observed during study time period (P < 0.05), indicating spatial autocorrelation in the spatial distribution of MT-ZVL. Hotspot and spatial autocorrelation analysis revealed clustering of infection cases in the Shaanxi-Shanxi border areas and in east of Shanxi province, where transmission increased rapidly over the study duration, as well as in well know high transmission areas in the south of Gansu province and the north of the Sichuan province. It indicates resurgence of MT-ZVL transmission over the latter three years of the study. Spatial clustering of infection was observed in localized areas, as well as sporadic outbreaks of infection.
| S-EPMC8016304 | biostudies-literature
Project description:Leishmania infantum is considered the predominant Leishmania species responsible for visceral leishmaniasis (VL) in Greece but limited molecular-typing-based studies have been performed so far. We retrospectively analyzed data and serum samples collected from 3661 individuals suspected for VL in a sixteen-year period, from 2005 to 2020, to study the seasonality and demographic characteristics of VL cases and to define the L. infantum genotypes circulating in the country. Serum samples were tested with immunofluorescence assay and/or molecular assay. qPCR Leishmania-positive samples were subjected to genotypic analysis based on polymorphisms in 12 microsatellite regions of the internal transcribed spacers (ITSs) 1 and 2. We diagnosed 219 definite (6%, sample with a positive molecular assay and/or antibody titer ≥ 1:400) and 230 probable (6.3%, sample with antibody titer between 1:100 and 1:200) VL cases. Data analysis revealed that amongst VL-definite cases, the age group (≥65) constitutes the most affected factor, since 36.9% of the VL cases belonged to this age group. Amongst the VL definite cases, the most frequently reported symptoms were fever (83%), splenomegaly (49%), and hepatomegaly (40%), but this was not the case for immunocompromised patients that developed non-typical symptoms of leishmaniasis. Although no statistically significant differences in the overall seasonality of VL cases were observed, February and June showed a significantly higher proportion of VL cases compared to August and December. Genotyping of ITS1 and ITS2 regions revealed that all VL cases belong to ITS type A of L. infantum. Our study provides epidemiological information on VL and demonstrates for the first time, providing genotypic data, the circulation of ITS type A L. infantum in Greece.
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Project description:Canine pathogens transmitted by blood-sucking arthropods are of significant importance for veterinary and, in some cases, human health. However, they are still underestimated and rarely investigated in many parts of the Mediterranean region, mostly due to financial reasons. Therefore, in the present paper, we investigated the occurrence of blood-associated pathogens affecting dogs in Crete, Greece. For this purpose, blood samples from 103 shelter dogs were screened for the pathogens by PCR and serological tests. Overall, samples from 43 dogs scored positive for at least one pathogen (41.8%). In particular, antibodies to Leishmania infantum were detected in 26 dogs (25.2%), and 15 and 11 animals were positive for Hepatozoon canis (14.6%) and Mycoplasma haemocanis (10.7%) by PCR, respectively. Co-infections were recorded in nine animals. Clinical signs indicative of infection (alterations of skin or coat or reduced body condition) were detected in 10 animals, four of which were infected with one pathogen, three with two pathogens. Based on the results obtained, dogs from Crete appear to be frequently exposed to several blood-borne pathogens, including agents of zoonotic concern. Given that some of the pathogens were reported for the first time in this area, results presented in our study should improve the awareness of the local veterinarians and of dog rescue organisations in order to reduce disease burden on stray and owned dogs and to control the spread of canine vector-borne diseases from Greece to non-endemic areas by travelling or exported infected dogs.
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Project description:Leishmania parasites cause outstanding levels of morbidity and mortality in many developing countries in tropical and subtropical regions. Numerous gene expression profiling studies have been performed comparing different Leishmania species' life-cycles and stage forms in regard to their distinct infective ability. Based on expression patterns, homology to human orthologues, in silico HLA-binding predictions, and annotated functions, we were able to select several vaccine candidates which are currently under study. One of these candidates is the Leishmania infantum ubiquitin-conjugating enzyme E2 (LiUBC1), whose relative levels, subcellular location, in vitro infectivity in the U937 myeloid human cell model, and protection levels in Syrian hamsters against L. infantum infection were studied herein. LiUBC1 displays a low level of similarity with the mammalian orthologs and relevant structure differences, such as the C-terminal domain, which is absent in the human ortholog. LiUBC1 is present in highly infective promastigotes. Knock-in parasites overexpressing the enzyme increased their infectivity, according to in vitro experiments. Syrian hamsters immunized with the recombinant LiUBC1 protein did not show any parasite burden in the spleen, unlike the infection control group. The IFN-γ transcript levels in splenocytes were significantly higher in the LiUBC1 immunized group. Therefore, LiUBC1 induced partial protection against L. infantum in the Syrian hamster model.
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Project description:Introduction: The armamentarium of antileishmanial drugs is small. It is further being threatened by the development of resistance and decreasing sensitivity to the available drugs. The development of newer drugs is sorely needed. Areas covered: The authors have based their review on a literature search performed using PubMed. The article specifically looks at investigational drugs, which have demonstrated, at the very least, in vitro and in vivo activities against the leishmania species that cause visceral leishmaniasis. Specifically, the authors review the nitroimidazole compound fexinidazole, which is one of the few drugs which have reached Phase II trials. The article also discusses the R enantiomer of (S)-PA-824, which has shown good antileishmanial activity. Finally, the article also highlights the many novel delivery systems and oral formulations of amphotericin B, which are both cheap and less toxic and are currently under investigation. Expert opinion: Very few new drugs have reached the clinic for this neglected tropical disease and there is an urgent need for new efficacious therapeutics. The authors believe that support from public-private partnerships would help in enabling the prompt development of drug candidates that could potentially make the clinic.
| S-EPMC4262729 | biostudies-other
Project description:BackgroundAs cases of visceral leishmaniasis (VL) in India dwindle, there is motivation to monitor elimination progress on a finer geographic scale than sub-district (block). Low-incidence projections across geographically- and demographically- heterogeneous communities are difficult to act upon, and equitable elimination cannot be achieved if local pockets of incidence are overlooked. However, maintaining consistent surveillance at this scale is resource-intensive and not sustainable in the long-term.MethodsWe analysed VL incidence across 45,000 villages in Bihar state, exploring spatial autocorrelation and associations with local environmental conditions in order to assess the feasibility of inference at this scale. We evaluated a statistical disaggregation approach to infer finer spatial variation from routinely-collected, block-level data, validating against observed village-level incidence.ResultsThis disaggregation approach does not estimate village-level incidence more accurately than a baseline assumption of block-homogeneity. Spatial auto-correlation is evident on a block-level but weak between neighbouring villages within the same block, possibly suggesting that longer-range transmission (e.g., due to population movement) may be an important contributor to village-level heterogeneity.ConclusionsIncreasing the range of reactive interventions to neighbouring villages may not improve their efficacy in suppressing transmission, but maintaining surveillance and diagnostic capacity in areas distant from recently observed cases - particularly along routes of population movement from endemic regions - could reduce reintroduction risk in currently unaffected villages. The reactive, spatially-targeted approach to VL surveillance limits interpretability of data observed at the village level, and hence the feasibility of routinely drawing and validating inference at this scale.
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Project description:Leishmania infantum causes potentially life-threatening disease in humans. To determine the extent of the animal reservoir for this pathogen in Bosnia and Herzegovina, we tested dogs and cats. We found that a large proportion of dogs were exposed to or infected with L. infantum, indicating endemicity in dogs and zoonotic risk for humans.
| S-EPMC6346464 | biostudies-literature