Modulation of Macrophage Redox and Apoptotic Processes to Leishmania infantum during Coinfection with the Tick-Borne Bacteria Borrelia burgdorferi.

Canine leishmaniosis (CanL) is a zoonotic disease caused by protozoan Leishmania infantum. Dogs with CanL are often coinfected with tick-borne bacterial pathogens, including Borrelia burgdorferi in the United States. These coinfections have been causally associated with hastened disease progression and mortality. However, the specific cellular mechanisms of how coinfections affect microbicidal responses against L. infantum are unknown. We hypothesized that B. burgdorferi coinfection impacts host macrophage effector functions, prompting L. infantum intracellular survival. In vitro experiments demonstrated that exposure to B. burgdorferi spirochetes significantly increased L. infantum parasite burden and pro-inflammatory responses in DH82 canine macrophage cells. Induction of cell death and generation of mitochondrial ROS were significantly decreased in coinfected DH82 cells compared to uninfected and L. infantum-infected cells. Ex vivo stimulation of PBMCs from L. infantum-seronegative and -seropositive subclinical dogs with spirochetes and/or total Leishmania antigens promoted limited induction of IFNγ. Coexposure significantly induced expression of pro-inflammatory cytokines and chemokines associated with Th17 differentiation and neutrophilic and monocytic recruitment in PBMCs from L. infantum-seropositive dogs. Excessive pro-inflammatory responses have previously been shown to cause CanL pathology. This work supports effective tick prevention and risk management of coinfections as critical strategies to prevent and control L. infantum progression in dogs.

Human rabies despite post-exposure prophylaxis: a systematic review of fatal breakthrough infections after zoonotic exposures.

Post-exposure prophylaxis (PEP) for rabies is widely administered and highly effective. Nevertheless, sporadic breakthrough infections (ie, rabies in people who have started PEP) have been reported. We conducted a systematic review of articles published between Jan 1, 1980 and June 1, 2022 to characterise breakthrough infections. After reviewing 3380 articles from across all continents, we identified 52 articles, which included a total of 122 breakthrough infections. We classified breakthrough infections on the basis of adherence to core practices (ie, wound cleaning and vaccine administration). Of 86 breakthrough infections with data, median time from exposure to symptom onset was 20 days (IQR 16-24). Most (89 [77%] of 115) participants received PEP within 2 days of an exposure. Severe wounds (defined as those involving multiple wound sites or bites to the head, face, or neck) were common (80 [69%] of 116 [with data]). Deviations from core practices were reported in 68 (56%) of 122 cases. Other possible causes for breakthrough infections included errors in the administration of rabies immunoglobulin, delays in seeking health care, and comorbidities or immunosuppression. Cold-chain integrity assessments and potency testing of PEP biologics were only rarely assessed (8 [7%] of 122 cases), neither of which were found to be a cause of breakthrough infections. Timely and appropriate administration of PEP is crucial to prevent rabies, and although people with high-risk exposures or immunosuppression can develop rabies despite adherence to core practices, this occurrence remains exceedingly rare.

Possibility of Leishmania Transmission via Lutzomyia spp. Sand Flies Within the USA and Implications for Human and Canine Autochthonous Infection.

Purpose of Review: Leishmaniasis is a leading cause of parasitic death, with incidence rising from decreased resources to administer insecticide and anti-leishmanial treatments due to the COVID-19 pandemic. Leishmaniasis is nonendemic in the United States (U.S.), but enzootic canine populations and potentially competent vectors warrant monitoring of autochthonous disease as a fluctuating climate facilitates vector expansion. Recent studies concerning sand fly distribution and vector capacity were assessed for implications of autochthonous transmission within the U.S. Recent Findings: Climate change and insecticide resistance provide challenges in sand fly control. While most Leishmania-infected dogs in the U.S. were infected via vertical transmission or were imported, autochthonous vector-borne cases were reported. Autochthonous vector-borne human cases have been reported in four states. Further vaccine research could contribute to infection control. Summary: Both cutaneous and visceral leishmaniasis cases in the U.S. are increasingly reported. Prevention measures including vector control and responsible animal breeding are critical to halt this zoonotic disease.

Assessing COVID-19 Pandemic Risk Perception and Response Preparedness in Veterinary and Animal Care Workers.

Veterinary and animal care workers perform critical functions in biosecurity and public health, yet little has been done to understand the unique needs and barriers these workers face when responding during a pandemic crisis. In this article, we evaluated the perceived risks and roles of veterinary and animal care workers during the COVID-19 pandemic and explored barriers and facilitators in their readiness, ability, and willingness to respond during a pandemic. We deployed a survey targeting US veterinary medical personnel, animal shelter and control workers, zoo and wildlife workers, and other animal care workers. Data were collected on respondents' self-reported job and demographic factors, perceptions of risk and job efficacy, and readiness, ability, and willingness to respond during the pandemic. We found that leadership roles and older age had the strongest association with decreased perceived risk and improved job efficacy and confidence, and that increased reported contact level with others (both coworkers and the public) was associated with increased perceived risk. We determined that older age and serving in leadership positions were associated with improved readiness, willingness, and ability to respond. Veterinary and animal care workers' dedication to public health response, reflected in our findings, will be imperative if more zoonotic vectors of SARS-CoV-2 arise. Response preparedness in veterinary and animal care workers can be improved by targeting younger workers not in leadership roles through support programs that focus on improving job efficacy and confidence in safety protocols. These findings can be used to target intervention and training efforts to support the most vulnerable within this critical, yet often overlooked, workforce.

Roles of traditional medicine and traditional healers for rabies prevention and potential impacts on post-exposure prophylaxis: A literature review.

INTRODUCTION: Globally, traditional medicine is widely used to treat a variety of injuries and illnesses, including dog bites, and exposures that are risky for rabies. However, efficacy of most traditional remedies used for rabies prevention or treatment has not been demonstrated in controlled trials or proven in community-based surveys. METHODS: Six databases were searched including the terms rabies, traditional treatment, traditional remedy, traditional therapy, traditional medicine, and medicinal treatment to review traditional remedies used in the prevention and treatment of rabies. In addition, published literature of rabies transmission dynamics was used to estimate statistical likelihood of dog bite victims developing rabies to provide clarity as to why traditional healers have a high apparent success rate when preventing death from rabies in victims bitten by suspected rabid dogs. RESULTS: Literature review yielded 50 articles, including three controlled experiments, that described use of traditional remedies for rabies prevention and treatment. Traditional remedies for rabies ranged from plant- or animal-based products to spiritual rituals; however, only a few controlled mice trials were conducted, and none of these trials demonstrated efficacy in preventing or treating rabies. Risk of dying from rabies after a bite from a dog with unknown rabies status is low, 1.90% (0.05%-29.60%). Therefore, traditional healers had a 98.10% (70.40%-99.95%) apparent success rate in preventing death from suspected rabid dog bites despite inefficaciousness of herbal remedies. CONCLUSION: There was no universal plant species or route of administration that was consistently used for rabies prevention or treatment across countries. No traditional remedy was efficacious in the prevention or treatment of rabies in randomized controlled experiments. Understanding the cultural context under which traditional remedies are used may facilitate collaboration of traditional healers with the modern medical system to ensure timely and appropriate use of proven therapies for prevention and clinical management of rabies.

Epidemiologic, Clinical and Immunological Consequences of Co-Infections during Canine Leishmaniosis.

Canine leishmaniosis (CanL) is a vector-borne, parasitic disease. CanL is endemic in the Mediterranean basin and South America but also found in Northern Africa, Asia, and the U.S. Regions with both competent sand fly vectors and L. infantum parasites are also endemic for additional infectious diseases that could cause co-infections in dogs. Growing evidence indicates that co-infections can impact immunologic responses and thus the clinical course of both CanL and the comorbid disease(s). The aim for this review is to summarize epidemiologic, clinical, and immunologic factors contributing to eight primary co-infections reported with CanL: Ehrlichia spp., Anaplasma spp., Borrelia spp., Babesia spp., Trypanosoma cruzi, Toxoplasma gondii, Dirofilaria immitis, Paracoccidioides braziliensis. Co-infection causes mechanistic differences in immunity which can alter diagnostics, therapeutic management, and prognosis of dogs with CanL. More research is needed to further explore immunomodulation during CanL co-infection(s) and their clinical impact.