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1. Data-driven predictions of potential Leishmania vectors in the Americas

   https://doi.org/10.1371/journal.pntd.0010749  

   Vadmal, Gowri M. ; Glidden, Caroline K. ; Han, Barbara A. ; Carvalho, Bruno M. ; Castellanos, Adrian A. ; Mordecai, Erin A. ( February 2023 , PLOS Neglected Tropical Diseases)

   McDowell, Mary Ann (Ed.)

   The incidence of vector-borne diseases is rising as deforestation, climate change, and globalization bring humans in contact with arthropods that can transmit pathogens. In particular, incidence of American Cutaneous Leishmaniasis (ACL), a disease caused by parasites transmitted by sandflies, is increasing as previously intact habitats are cleared for agriculture and urban areas, potentially bringing people into contact with vectors and reservoir hosts. Previous evidence has identified dozens of sandfly species that have been infected with and/or transmit Leishmania parasites. However, there is an incomplete understanding of which sandfly species transmit the parasite, complicating efforts to limit disease spread. Here, we apply machine learning models (boosted regression trees) to leverage biological and geographical traits of known sandfly vectors to predict potential vectors. Additionally, we generate trait profiles of confirmed vectors and identify important factors in transmission. Our model performed well with an average out of sample accuracy of 86%. The models predict that synanthropic sandflies living in areas with greater canopy height, less human modification, and within an optimal range of rainfall are more likely to be Leishmania vectors. We also observed that generalist sandflies that are able to inhabit many different ecoregions are more likely to transmit the parasites. Our results suggest that Psychodopygus amazonensis and Nyssomia antunesi are unidentified potential vectors, and should be the focus of sampling and research efforts. Overall, we found that our machine learning approach provides valuable information for Leishmania surveillance and management in an otherwise complex and data sparse system. 

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2. Disruption of the Putative Ribosome-Binding Motif of a Scaffold Protein Impairs Cytochrome c Oxidase Subunit Expression in Leishmania major

   https://doi.org/10.1128/mSphere.00644-18  

   Cardenas, Daviel ; Sylvester, Charity ; Cao, Bo ; Nation, Catherine S. ; Pizarro, Juan C. ; Lu, Hua ; Guidry, Jessie ; Wojcik, Edward J. ; Kelly, Ben L. ( April 2019 , mSphere)

   Moreno, Silvia N. (Ed.)

   ABSTRACT During their parasitic life cycle, through sandflies and vertebrate hosts, Leishmania parasites confront strikingly different environments, including abrupt changes in pH and temperature, to which they must rapidly adapt. These adaptations include alterations in Leishmania gene expression, metabolism, and morphology, allowing them to thrive as promastigotes in the sandfly and as intracellular amastigotes in the vertebrate host. A critical aspect of Leishmania metabolic adaptation to these changes is maintenance of efficient mitochondrial function in the hostile vertebrate environment. Such functions, including generation of ATP, depend upon the expression of many mitochondrial proteins, including subunits of cytochrome c oxidase (COX). Significantly, under mammalian temperature conditions, expression of Leishmania major COX subunit IV (LmCOX4) and virulence are dependent upon two copies of LACK , a gene that encodes the ribosome-associated scaffold protein, LACK ( Leishmania ortholog of RACK1 [receptor for activated C kinase]). Targeted replacement of an endogenous LACK copy with a putative ribosome-binding motif-disrupted variant (LACK R34D35G36 →LACK D34D35E36 ) resulted in thermosensitive parasites that showed diminished LmCOX4 expression, mitochondrial fitness, and replication in macrophages. Surprisingly, despite these phenotypes, LACK D34D35E36 associated with monosomes and polysomes and showed no major impairment of global protein synthesis. Collectively, these data suggest that wild-type (WT) LACK orchestrates robust LmCOX4 expression and mitochondrial fitness to ensure parasite virulence, via optimized functional interactions with the ribosome. IMPORTANCE Leishmania parasites are trypanosomatid protozoans that persist in infected human hosts to cause a spectrum of pathologies, from cutaneous and mucocutaneous manifestations to visceral leishmaniasis caused by Leishmania donovani . The latter is usually fatal if not treated. Persistence of L. major in the mammalian host depends upon maintaining gene-regulatory programs to support essential parasite metabolic functions. These include expression and assembly of mitochondrial L. major cytochrome c oxidase (LmCOX) subunits, important for Leishmania ATP production. Significantly, under mammalian conditions, WT levels of LmCOX subunits require threshold levels of the Leishmania ribosome-associated scaffold protein, LACK. Unexpectedly, we find that although disruption of LACK’s putative ribosome-binding motif does not grossly perturb ribosome association or global protein synthesis, it nonetheless impairs COX subunit expression, mitochondrial function, and virulence. Our data indicate that the quality of LACK’s interaction with Leishmania ribosomes is critical for LmCOX subunit expression and parasite mitochondrial function in the mammalian host. Collectively, these findings validate LACK’s ribosomal interactions as a potential therapeutic target. 

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3. Macro-parasites and micro-parasites co-exist in rodent communities but are associated with different community-level parameters

   https://doi.org/10.1016/j.ijppaw.2023.08.006  

   Salomon, Jordan ; Sambado, Samantha B. ; Crews, Arielle ; Sidhu, Sukhman ; Seredian, Eric ; Almarinez, Adrienne ; Grgich, Rachel ; Swei, Andrea ( August 2023 , International Journal for Parasitology: Parasites and Wildlife)

   Wildlife species are often heavily parasitized by multiple infections simultaneously. Yet research on sylvatic transmission cycles, tend to focus on host interactions with a single parasite and neglects the influence of co- infections by other pathogens and parasites. Co-infections between macro-parasites and micro-parasites can alter mechanisms that regulate pathogenesis and are important for understanding disease emergence and dy- namics. Wildlife rodent hosts in the Lyme disease system are infected with macro-parasites (i.e., ticks and hel- minths) and micro-parasites (i.e., Borrelia spp.), however, there has not been a study that investigates the interaction of all three parasites (i.e., I. pacificus, Borrelia spp., and helminths) and how these co-infections impact prevalence of micro-parasites. We live-trapped rodents in ten sites in northern California to collect feces, blood, ear tissue, and attached ticks. These samples were used to test for infection status of Borrelia species (i.e., micro- parasite), and describe the burden of ticks and helminths (i.e., macro-parasites). We found that some rodent hosts were co-infected with all three parasites, however, the burden or presence of concurrent macro-parasites were not associated with Borrelia infections. For macro-parasites, we found that tick burdens were positively associ- ated with rodent Shannon diversity while negatively associated with predator diversity, whereas helminth burdens were not significantly associated with any host community metric. Ticks and tick-borne pathogens are associated with rodent host diversity, predator diversity, and abiotic factors. However, it is still unknown what factors helminths are associated with on the community level. Understanding the mechanisms that influence co- infections of multiple types of parasites within and across hosts is an increasingly critical component of characterizing zoonotic disease transmission and maintenance. 

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4. Amplification of pathogenic Leptospira infection with greater abundance and co‐occurrence of rodent hosts across a counter‐urbanizing landscape

   https://doi.org/10.1111/mec.15710  

   Peterson, Anna C. ; Ghersi, Bruno M. ; Riegel, Claudia ; Wunder, Jr, Elsio A. ; Childs, James E. ; Blum, Michael J. ( November 2020 , Molecular Ecology)

   Land use change can elevate disease risk by creating conditions beneficial to species that carry zoonotic pathogens. Observations of concordant global trends in increased pathogen prevalence or disease incidence and landscape change have generated concerns that urbanization could increase transmission risk of some pathogens. Yet host–pathogen relationships underlying transmission risk have not been well characterized within cities, even where contact between humans and species capable of transmitting pathogens of concern occurs. We addressed this deficit by testing the hypothesis that areas in cities experiencing greater population loss and infrastructure decline (i.e., counter‐urbanization) can support a greater diversity of host species and a larger and more diverse pool of pathogens. We did so by characterizing pathogenicLeptospirainfection relative to rodent host richness and abundance across a mosaic of abandonment in post‐Katrina New Orleans (Louisiana, USA). We found thatLeptospirainfection loads were highest in areas that harboured increased rodent species richness (which ranged from one to four rodent species detected). Areas with greater host co‐occurrence also harboured a greater abundance of hosts, including the host species most likely to carry high infection loads, indicating thatLeptospirainfection can be amplified by increases in overall and relative host abundance. Evidence of shared infection among rodent host species indicates that cross‐species transmission ofLeptospiraprobably increases infection at sites with greater host richness. Additionally, evidence that rodent co‐occurrence and abundance andLeptospirainfection load parallel abandonment suggests that counter‐urbanization can elevate zoonotic disease risk within cities, particularly in underserved communities that are burdened with disproportionate concentrations of derelict properties.

    

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5. Linking Lyme disease ecology and epidemiology: reservoir host identity, not richness, determines tick infection and human disease in California

   https://doi.org/10.1088/1748-9326/ac9ece  

   MacDonald, Andrew J ; McComb, Sofie ; Sambado, Samantha ( November 2022 , Environmental Research Letters)

   Abstract Understanding the community ecology of vector-borne and zoonotic diseases, and how it may shift transmission risk as it responds to environmental change, has become a central focus in disease ecology. Yet, it has been challenging to link the ecology of disease with reported human incidence. Here, we bridge the gap between local-scale community ecology and large-scale disease epidemiology, drawing from a priori knowledge of tick-pathogen-host ecology to model spatially-explicit Lyme disease (LD) risk, and human Lyme disease incidence (LDI) in California. We first use a species distribution modeling approach to model disease risk with variables capturing climate, vegetation, and ecology of key reservoir host species, and host species richness. We then use our modeled disease risk to predict human disease incidence at the zip code level across California. Our results suggest the ecology of key reservoir hosts—particularly dusky-footed woodrats—is central to disease risk posed by ticks, but that host community richness is not strongly associated with tick infection. Predicted disease risk, which is most strongly influenced by the ecology of dusky-footed woodrats, in turn is a strong predictor of human LDI. This relationship holds in the Wildland-Urban Interface, but not in open access public lands, and is stronger in northern California than in the state as a whole. This suggests peridomestic exposure to infected ticks may be more important to LD epidemiology in California than recreational exposure, and underlines the importance of the community ecology of LD in determining human transmission risk throughout this LD endemic region of far western North America. More targeted tick and pathogen surveillance, coupled with studies of human and tick behavior could improve understanding of key risk factors and inform public health interventions. Moreover, longitudinal surveillance data could further improve forecasts of disease risk in response to global environmental change. 

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