A Systemic Review of the Frequency of Animal Leptospirosis in the Southern United States and the Implications for Human Health

Leptospirosis is a zoonotic disease with symptoms in humans and animals, ranging from subclinical to serious and fatal. The disease occurs worldwide, but there is limited recognition of the public and animal health risks it poses in the southern United States. A systematic review of the frequency of animal leptospirosis in 17 states and jurisdictions covering the southern continental United States was performed to advance our understanding of the pathogen's distribution and identify transmission patterns that could be targeted for prevention efforts. Fifty-two articles, spanning >100 years, met the analysis criteria. A wide range of techniques were used to measure seroprevalence and isolate the bacteria. The assessment identified exposure to Leptospira spp and Leptospira spp infection among a diverse range of species, spanning 22 animal families within 14 states, suggesting that the pathogen is distributed throughout the southern region. Disease frequency trends were assessed among animals in various habitats (all habitats, nonwild habitats, and wild habitats). The frequency of Leptospira spp detection in animals in wild habitats increased slightly over time (<0.2%/year). We identified reports of 11 human leptospirosis illness clusters and outbreaks in the southern United States. Exposure to potentially contaminated surface waters were documented for at least seven of the events, and interactions with infected or likely infected animals were documented for at least six of the events. This analysis highlights the need for stronger partnerships across the public and animal health fields to enhance diagnostics, surveillance, and reporting. The early identification of leptospirosis in animals may serve as an indicator of environmental contamination and trigger prevention measures, such as vaccinating companion animals and livestock, use of potable water, and the wearing of waterproof protective clothing near water that may be contaminated

MLL-AF9-Induced Leukemogenesis Requires Coexpression of the Wild-Type Mll Allele

National Institutes of Health [R01 CA113962]; Leukemia and Lymphoma Society; T32 training [CA09140]Oncogenic fusion proteins are capable of initiating tumorigenesis, but the role of their wild-type counterparts in this process is poorly understood. The mixed lineage leukemia (MLL) gene undergoes chromosomal translocations, resulting in the formation of oncogenic MILL fusion proteins (MLL-FPs). Here, we show that menin recruits both wild-type MLL and oncogenic MLL-AF9 fusion protein to the loci of HOX genes to activate their transcription. Wild-type MLL not only catalyzes histone methylation at key target genes but also controls distinct MLL-AF9-induced histone methylation. Notably, the wild-type MY allele is required for MLL-AF9-induced leukemogenesis and maintenance of MLL-AF9-transformed cells. These findings suggest an essential cooperation between an oncogene and its wild-type counterpart in MLL-AF9-induced leukemogenesis

MLL-AF9-Induced Leukemogenesis Requires Coexpression of the Wild-Type Mll Allele

National Institutes of Health [R01 CA113962]; Leukemia and Lymphoma Society; T32 training [CA09140]Oncogenic fusion proteins are capable of initiating tumorigenesis, but the role of their wild-type counterparts in this process is poorly understood. The mixed lineage leukemia (MLL) gene undergoes chromosomal translocations, resulting in the formation of oncogenic MILL fusion proteins (MLL-FPs). Here, we show that menin recruits both wild-type MLL and oncogenic MLL-AF9 fusion protein to the loci of HOX genes to activate their transcription. Wild-type MLL not only catalyzes histone methylation at key target genes but also controls distinct MLL-AF9-induced histone methylation. Notably, the wild-type MY allele is required for MLL-AF9-induced leukemogenesis and maintenance of MLL-AF9-transformed cells. These findings suggest an essential cooperation between an oncogene and its wild-type counterpart in MLL-AF9-induced leukemogenesis