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Zoonotic canine leishmaniosis, caused by Leishmania infantum , is a fatal disease worldwide in both humans and the reservoir host, dogs. The primary route of transmission is via sand fly bite. Vertical, transplacental, transmission of L. infantum to offspring has been shown to be critical for maintenance of infection in both endemic and non-endemic areas. In the United States, canine leishmaniosis (CanL) is enzootic within hunting dog populations. Previous work with US hunting dogs found that transplacental transmission of L. infantum occurs frequently with high infectivity. Dogs born to CanL infected mothers were almost fourteen times more likely to become positive for L. infantum over their lifetime. Globally, public health agencies control CanL through canine and human case detection and treatment, and in some cases dog culling and reducing vector populations. There is no specific strategy to control vertical transmission of CanL. A previous randomized field trial in US hunting dogs found that a Leishmania A2 protein, saponin-adjuvanted, vaccine (LeishTec) used as an immunotherapy, significantly reduced the risk of progression to clinically overt leishmaniasis by 30% in asymptomatic dogs. It is unknown whether maternal vaccination could inhibit infection risk in her offspring. We hypothesized that dogs born to infected and vaccinated dams would be less likely to test diagnostically positive via L. infantum specific kqPCR or serology compared to dogs born to infected unvaccinated mothers. A population of dogs born to L. infantum infected dams were evaluated to assess LeishTec vaccination to prevent transmission to offspring. Dogs born to unvaccinated, L. infantum infected, dams had higher mortality (12.50% vs 0.00%), higher likelihood of clinical disease (94.12% vs 59.00%) and were more likely to be diagnostically positive for CanL (22.22% vs 4.55%). Vaccination of dams already infected prior to pregnancy greatly reduced the risk of transplacental transmission of L. infantum . Incorporating vertical transmission prevention as a public health intervention in countries where Leishmania is endemic could aid in infection control.

Background Both incidence and geographical range of tick-borne disease has increased across the USA. Similar to people, dogs are hosts for Anaplasma spp., Babesia spp., Ehrlichia spp. and Borrelia burgdorferi. Dogs also share our homes and beds, making them both a sentinel for the ticks in our backyards but also increasing our exposure to ticks. Measures to better track, prevent, and/or treat tick-borne diseases in companion animals can lead to better control and prevention of human tick-borne disease. This study identifies demographic and co-infection risk factors for canine seropositivity to tick-borne infections in a cohort of hunting dogs across the USA. Results Human patterns of tick-borne disease co-infection in the USA have been predominantly driven by the geographical distribution of the tick vector. Dogs who tested seropositive for Anaplasma spp. were 1.40 times more likely ( P = 0.0242) to also test seropositive for Babesia spp. and vice versa (1.60 times more likely, P = 0.0014). Dogs living in the West had 5% lower risk ( P = 0.0001) for Ehrlichia spp. seropositivity compared to other regions. Controlling for age and Anaplasma spp. seroprevalence, dogs in all three other regions were 2.30 times more likely ( P = 0.0216) to test seropositive for B. burgdorferi than dogs in the West. Dogs seropositive for B. burgdorferi were 1.60 times more likely ( P = 0.0473) to be seropositive for Anaplasma spp. Conclusions Tick geographical distributions have a prominent impact on the regional distribution of hunting dog exposure to tick-borne diseases. Education concerning regional tick prevalence and disease risk is important for everyone, but particularly dog owners, regarding ticks in their region and protection from infection and co-infection of tick-borne pathogens as they travel or move with their dogs. Dogs are sentinel species for human exposure to ticks, and as such surveillance of canine tick-borne infections and understanding the probability that these infections might be seen together as co-infections helps predict emerging areas where people are more likely to be exposed as well.

Background Visceral leishmaniasis (VL) is a vector borne zoonotic disease endemic in humans and dogs in Brazil. Due to the increased risk of human infection secondary to the presence of infected dogs, public health measures in Brazil mandate testing and culling of infected dogs. Despite this important relationship between human and canine infection, little is known about what makes the dog reservoir progress to clinical illness, significantly tied to infectiousness to sand flies. Dogs in endemic areas of Brazil are exposed to many tick-borne pathogens, which are likely to alter the immune environment and thus control of L. infantum . Results A cross-sectional study of 223 dogs from an area of Natal, in the Rio Grande do Norte, Brazil, were studied to determine the association between comorbid tick-borne disease and Leishmania infection in this endemic area. The risk of Leishmania seropositivity was 1.68× greater in dogs with tick-borne disease seropositivity compared to those without (Adjusted RR: 1.68, 95% CI: 1.09–2.61, P = 0.019). A longitudinal study of 214 hunting dogs in the USA was conducted to determine the causal relationship between infection with tick-borne diseases and progression of VL. Hunting dogs were evaluated three times across a full tick season to detect incident infection with tick-borne diseases. A logistic regression model with generalized estimating equations to estimate the parameters was used to determine how exposure to tick-borne disease altered VL progression over these three time points when controlling for other variables. Dogs infected with three or more tick-borne diseases were 11× more likely to be associated with progression to clinical VL than dogs with no tick-borne disease (Adjusted RR: 11.64, 95% CI: 1.22–110.99, P = 0.03). Dogs with exposure to both Leishmania spp. and tick-borne diseases were five times more likely to die during the study period (RR: 4.85, 95% CI: 1.65–14.24, P = 0.0051). Conclusions Comorbid tick-borne diseases dramatically increased the likelihood that a dog had clinical L. infantum infection, making them more likely to transmit infection to sand flies and people. As an important consequence, reduction of tick-borne disease exposure through topical or oral insecticides may be an important way to reduce progression and transmissibility of Leishmania infection from the canine reservoir to people.

•Blinded clinical field trial.•Anti-Leishmania vaccine as immunotherapy significantly reduced clinical progression.•Vaccine decreased mortality in Leishmania infantum-infected, healthy, dogs. Better tools are necessary to eliminate visceral leishmaniasis (VL). Modeling studies for regional Leishmania elimination indicate that an effective vaccine is a critical tool. Dogs are the reservoir host of L. infantum in Brazil and the Mediterranean basin, and therefore are an important target for public health interventions as well as a relevant disease model for human VL. No vaccine has been efficacious as an immunotherapy to prevent progression of already diagnostically positive individuals to symptomatic leishmaniasis. We performed a double-blinded, block-randomized, placebo-controlled, vaccine immunotherapy trial testing the efficacy of a recombinant Leishmania A2 protein, saponin-adjuvanted, vaccine, LeishTec®, in owned hunting dogs infected with L. infantum. The primary outcome was reduction of clinical progression, with reduction of mortality as a secondary outcome. Vaccination as an immunotherapy reduced the risk of progression to clinically overt leishmaniasis by 25% in asymptomatic dogs (RR: 1.33 95% C.I. 1.009–1.786 p-value: 0.0450). Receiving vaccine vs. placebo reduced all-cause mortality in younger asymptomatic dogs by 70% (RR: 3.19 95% C.I.: 1.185–8.502 p-value = 0.0245). Vaccination of infected-healthy animals with an anti-Leishmania vaccine significantly reduced clinical progression and decreased all-cause mortality. Use of vaccination in infected-healthy dogs can be a tool for Leishmania control.

Infection with Leishmania causes diseases with variable presentation. The most severe form is visceral leishmaniasis (VL), caused by either L. donovani or L. infantum . Despite efforts to eliminate VL, to date, molecular detection in resource-poor settings have lacked the accuracy and rapidity that would enable widespread field use and the need for accurate, sensitive assays to detect asymptomatic Leishmania infection has become apparent. The domestic dog serves as the primary reservoir host of L. infantum . Study of this reservoir population provides an opportunity to evaluate the sensitivity and specificity of diagnostics for well-defined, symptomatic, canine visceral leishmaniasis (CVL) and asymptomatic L. infantum infection. Blood samples from an L. infantum -endemic population of US hunting dogs were evaluated with Dual-Path Platform (DPP®) CVL compared to those obtained via direct detection methods (culture- and Leishmania -specific quantitative polymerase chain reaction, qPCR) and immunofluorescence anti- Leishmania antibody test (IFAT). Statistically significant correlations were found between DPP® CVL development time and clinical status, culture status, circulating DNA levels, and IFAT titer. DPP® CVL results correlated with both clinical severity of disease and serological evidence of asymptomatic L. infantum infection. By precisely documenting the minimum time required for the development of a clear positive result in DPP® CVL, this test could be used in a rapid, semi-quantitative manner for the evaluation of asymptomatic and symptomatic CVL. Our results also indicate that a similar test could be used to improve our understanding of human VL.

Infection with Leishmania causes diseases with variable presentation. The most severe form is visceral leishmaniasis (VL), caused by either L. donovani or L. infantum. Despite efforts to eliminate VL, to date, molecular detection in resource-poor settings have lacked the accuracy and rapidity that would enable widespread field use and the need for accurate, sensitive assays to detect asymptomatic Leishmania infection has become apparent. The domestic dog serves as the primary reservoir host of L. infantum. Study of this reservoir population provides an opportunity to evaluate the sensitivity and specificity of diagnostics for well-defined, symptomatic, canine visceral leishmaniasis (CVL) and asymptomatic L. infantum infection. Blood samples from an L. infantum-endemic population of US hunting dogs were evaluated with Dual-Path Platform (DPP registered ) CVL compared to those obtained via direct detection methods (culture- and Leishmania-specific quantitative polymerase chain reaction, qPCR) and immunofluorescence anti-Leishmania antibody test (IFAT). Statistically significant correlations were found between DPP registered CVL development time and clinical status, culture status, circulating DNA levels, and IFAT titer. DPP registered CVL results correlated with both clinical severity of disease and serological evidence of asymptomatic L. infantum infection. By precisely documenting the minimum time required for the development of a clear positive result in DPP registered CVL, this test could be used in a rapid, semi-quantitative manner for the evaluation of asymptomatic and symptomatic CVL. Our results also indicate that a similar test could be used to improve our understanding of human VL.

\"[Harry Potter] and the Sorcerer's Stone\" is the book that started the worldwide Potter craze. And after an hour or more of waiting, it's time to step into the eighth-floor auditorium and into England, home to Harry Potter and Company. Dayton's takes you through the book from beginning to end, displaying key scenes. You'll see when Harry is first dropped off at the home of his uncle, who is a Muggle (a non-wizard). When Harry is 10, he discovers that he is a wizard and is enrolled at Hogwart's school.

Ecologists have worked to ascribe function to the variation found in plant populations, communities and ecosystems across environments for at least the past century. The vast body of research in functional ecology has drastically improved understanding of how individuals respond to their environment, communities are assembled and ecosystems function. However, with limited exceptions, few studies have quantified differences in plant function during the earliest stages of the plant life cycle, and fewer have tested how this early variability shapes populations, communities and ecosystems. Drawing from the literature and our collective experience, we describe the current state of knowledge in seedling functional ecology and provide examples of how this subdiscipline can enrich our fundamental understanding of plant function across levels of organisation. To inspire progressive work in this area, we also outline key considerations involved in seedling functional research (who, what, when, where and how to measure seedling traits) and identify remaining challenges and gaps in understanding around methodological approaches. Within this conceptual synthesis, we highlight three critical areas in seedling ecology for future research to target. First, given wide variation in the definition of a ‘seedling’, we provide a standard definition based on seed reserve dependence while emphasising the need to measure ontogenetic variation more clearly both within and following the seedling stage. Second, studies demonstrate that seedlings can be studied in multiple media (e.g. soil, agar, filter paper) and conditions (e.g. field, greenhouse, laboratory). We recommend that researchers select methods based on explicit goals, yet follow standard guidelines to reduce methodological noise across studies. Third, research is critically needed to assess the implications of different methodologies on trait measurement and compatibility across studies. By highlighting the importance of seedling functional ecology and suggesting pathways to address key challenges, we aim to inspire future research that generates useful and comparable data on seedling functional ecology. This work is critical to explain variation within and among populations, communities and ecosystems and integrate this most vulnerable stage of plant life into ecological frameworks.

Plasmodium falciparum , the most virulent agent of human malaria, shares a recent common ancestor with the gorilla parasite Plasmodium praefalciparum . Little is known about the other gorilla- and chimpanzee-infecting species in the same ( Laverania ) subgenus as P. falciparum , but none of them are capable of establishing repeated infection and transmission in humans. To elucidate underlying mechanisms and the evolutionary history of this subgenus, we have generated multiple genomes from all known Laverania species. The completeness of our dataset allows us to conclude that interspecific gene transfers, as well as convergent evolution, were important in the evolution of these species. Striking copy number and structural variations were observed within gene families and one, stevor , shows a host-specific sequence pattern. The complete genome sequence of the closest ancestor of P. falciparum enables us to estimate the timing of the beginning of speciation to be 40,000–60,000 years ago followed by a population bottleneck around 4,000–6,000 years ago. Our data allow us also to search in detail for the features of P. falciparum that made it the only member of the Laverania able to infect and spread in humans. Sequencing of gorilla- and chimpanzee-infecting Plasmodium species elucidates the evolutionary history of the Laverania subgenus and highlights features of the human-infecting Plasmodium falciparum species that enable parasite transmission in humans.

BackgroundAlthough the incidence of Clostridium difficile infection (CDI) is increasing, available CDI treatment options are limited in terms of sustained response after treatment. This phase 3 trial assessed the efficacy and safety of surotomycin, a novel bactericidal cyclic lipopeptide, versus oral vancomycin in subjects with CDI.MethodsIn this randomized, double-blind, active-controlled, multicenter, international trial, subjects with CDI confirmed by a positive toxin result were randomized to receive surotomycin (250 mg twice daily) or vancomycin (125 mg 4 times daily) orally for 10 days. The primary endpoints were clinical response at end of treatment and evaluation of surotomycin safety. The key secondary endpoints were clinical response over time and sustained clinical response through a 30- to 40-day follow-up period. Clostridium difficile infection recurrence during follow-up and time to diarrhea resolution were also analyzed.ResultsIn total, 570 subjects were randomized and had confirmed CDI; 290 subjects received surotomycin and 280 subjects received vancomycin. Surotomycin clinical cure rates at end of treatment (surotomycin/vancomycin: 79.0%/83.6%; difference of −4.6%; 95% confidence interval, −11.0 to 1.9]), clinical response over time (stratified log-rank test, P = .832), and sustained clinical response at end of trial (Day 40–50) (60.6%/61.4%; difference of −0.8%; 95% CI, −8.8 to 7.1) in the microbiological modified intent to treat population did not meet noninferiority or superiority criteria versus vancomycin. Both treatments were generally well tolerated.ConclusionsSurotomycin failed to meet the criteria for noninferiority versus vancomycin for the primary and key secondary endpoints in this trial.