Search

As part of public health preparedness for infectious disease threats, CDC collaborates with other U.S. public health officials to ensure that the Laboratory Response Network (LRN) has diagnostic tools to detect Orthopoxviruses, the genus that includes Variola virus, the causative agent of smallpox. LRN is a network of state and local public health, federal, U.S. Department of Defense (DOD), veterinary, food, and environmental testing laboratories. CDC developed, and the Food and Drug Administration (FDA) granted 510(k) clearance* for the Non-variola Orthopoxvirus Real-time PCR Primer and Probe Set (non-variola Orthopoxvirus [NVO] assay), a polymerase chain reaction (PCR) diagnostic test to detect NVO. On May 17, 2022, CDC was contacted by the Massachusetts Department of Public Health (DPH) regarding a suspected case of monkeypox, a disease caused by the Orthopoxvirus Monkeypox virus. Specimens were collected and tested by the Massachusetts DPH public health laboratory with LRN testing capability using the NVO assay. Nationwide, 68 LRN laboratories had capacity to test approximately 8,000 NVO tests per week during June. During May 17-June 30, LRN laboratories tested 2,009 specimens from suspected monkeypox cases. Among those, 730 (36.3%) specimens from 395 patients were positive for NVO. NVO-positive specimens from 159 persons were confirmed by CDC to be monkeypox; final characterization is pending for 236. Prompt identification of persons with infection allowed rapid response to the outbreak, including isolation and treatment of patients, administration of vaccines, and other public health action. To further facilitate access to testing and increase convenience for providers and patients by using existing provider-laboratory relationships, CDC and LRN are supporting five large commercial laboratories with a national footprint (Aegis Science, LabCorp, Mayo Clinic Laboratories, Quest Diagnostics, and Sonic Healthcare) to establish NVO testing capacity of 10,000 specimens per week per laboratory. On July 6, 2022, the first commercial laboratory began accepting specimens for NVO testing based on clinician orders.

Simple Summary Neospora caninum causes abortion and other reproductive challenges in livestock and leads to large economic losses every year. Wild pigs were evaluated for their potential role in the transmission of N. caninum, the parasite that causes neosporosis in cattle and other animals. Three assays were used to identify past or current exposure to N. caninum in wild pigs and histology was performed to determine if there was a pathology consistent with a N. caninum infection in the tissues that were evaluated. The following assays reported positive results: Kit A—67.8%, Kit B—12.5%, Indirect Fluorescent Antibody Test—84.1%, and Histology—0%. Importantly, the assays used in this study were not congruent with all duplicate samples or between test types and demonstrate the need for a more reliable test to identify N. caninum infections in wild pigs to better assess their potential role in disease transmission. Abstract Neospora caninum is a protozoan parasite, reported as a leading cause of cattle abortions and reproductive failure worldwide, costing the cattle industry approximately $1.3 billion annually. With wild pig (Sus scrofa) populations estimated at over six million in the United States, contact between wild pigs and livestock is inevitable, mainly because of the widespread geographic co-occurrence of the two species. As a known reservoir for numerous fungal, bacterial, viral and parasitic diseases, wild pigs are of particular importance for human and veterinary health relative to the prevention of infectious diseases. The seroprevalence of N. caninum in wild pig populations was previously documented in the United States, raising the question as to their exposure point of prevalence. This research screened 116 individual wild pigs for N. caninum using a variety of available assays. Using two different commercially available ELISA test kits, seroprevalence ranged from 12.5% to 67.8%. The Indirect Fluorescent Antibody Test resulted in our highest percent seroprevalence for these samples, at 84.1%. However, none of our samples showed any presence of N. caninum or associated pathologies via histological evaluation of representative tissues. Importantly, the assays used in this study were not congruent with all duplicate samples or between the test types used. The implications of these non-congruent results demonstrates that currently available testing assays produce variable results, underscoring the need for more reliable testing kits and a standardized methodology when assessing disease prevalence in wildlife, particularly for N. caninum in wild pigs, which impacts prevalence and comparability across studies.

The authors suggest that healthcare practitioners’ consideration of vector-borne and/or zoonotic disease is largely dependent on the scope and specificity of education received during and after their professional training. They further suggest that this training is desperately lacking in the medical field and needs to be addressed., Objective Recognition and reporting of vector-borne and zoonotic disease (VBZD) cases is largely dependent upon the consideration of such diseases by healthcare practitioners during the initial diagnosis and ordering of specific confirmative diagnostic tests. This study was conducted to assess the general knowledge and understanding of VBZD transmission and clinical presentation. Methods Healthcare practitioners were surveyed to determine the extent of training and educational experiences they received relative to VBZDs, and their likelihood to consider such diseases during differential diagnoses. In addition, an assessment of their knowledge of arthropod species that may transmit VBZD pathogens was conducted. Results Having postprofessional school training relevant to VBZDs significantly influenced diagnostic accuracy for such disease cases based on the presented clinical signs and symptoms. Conclusions The prevalence of VBZDs in the United States likely is significantly underestimated. The authors suggest the enhancement of VBZD-focused education as an important initiative that would significantly improve timely diagnosis, treatment, and, ultimately, prevention of these diseases.

Summary: Despite remarkable developments in healthcare, the world was not ready to stop the spread of the novel COVID-19 pandemic almost a century after the great influenza pandemic. The explosive increase in the number of patients stalled the healthcare system, and the first and apparent issue was the shortage of personal protective equipment (PPE). Our group established a system using a hydrogen peroxide vaporization method to decontaminate and reuse N95 respirators for healthcare workers. The system decontaminated over 12,000 units of PPE to cover institutions in West Texas. This service provided support at the most needed time during the pandemic.

Wild pig (Sus scrofa) populations in the United States are expanding and increasing in distribution and abundance and are known to reservoir a variety of pathogens that can have economic and agricultural impacts. We examined wild pigs for exposure to Brucella spp. and Francisella tularensis from Oklahoma and Texas to determine their potential role as a regional reservoir for these pathogens since wild pigs co‐occur with livestock, especially on rangelands in this region. Antibodies to Brucella spp. and F. tularensis were found in every location sampled and during multiple years. Overall, wild pigs had a 12.5% prevalence of Brucella spp. and a 14.8% prevalence of F. tularensis in this study. Wild pig prevalence of Brucella spp. was 43 times higher in southcentral Oklahoma compared to previously published results. Understanding and monitoring regional disease prevalence rates in wild pigs are necessary, especially on rangelands managing for livestock that may be susceptible to these diseases.

The intestinal mucosal surface in all vertebrates is exposed to enormous numbers of microorganisms that include bacteria, archaea, fungi and viruses. Coexistence of the host with the gut microbiota represents an active and mutually beneficial relationship that helps to shape the mucosal and systemic immune systems of both mammals and teleosts (ray-finned fish). Due to the potential for enteric microorganisms to invade intestinal tissue and induce local and/or systemic inflammation, the mucosal immune system has developed a number of protective mechanisms that allow the host to mount an appropriate immune response to invading bacteria, while limiting bystander tissue injury associated with these immune responses. Failure to properly regulate mucosal immunity is thought to be responsible for the development of chronic intestinal inflammation. The objective of this review is to present our current understanding of the role that intestinal bacteria play in vertebrate health and disease. While our primary focus will be humans and mice, we also present the new and exciting comparative studies being performed in zebrafish to model host-microbe interactions.

Animal models of disease have been used extensively by the research community for the past several decades to better understand the pathogenesis of different diseases as well as assess the efficacy and toxicity of different therapeutic agents. Retrospective analyses of numerous preclinical intervention studies using mouse models of acute and chronic inflammatory diseases reveal a generalized failure to translate promising interventions or therapeutics into clinically-effective treatments in patients. Although several possible reasons have been suggested to account for this generalized failure to translate therapeutic efficacy from the laboratory bench to the patient’s bedside, it is becoming increasingly apparent that the mouse immune system may not adequately recapitulate the immuno-pathological mechanisms observed in human diseases. Indeed, it is well-known that >80 major differences exist between mouse and human immunology; all of which contribute to significant differences in immune system development, activation and responses to challenges in innate and adaptive immunity. This inconvenient reality has prompted investigators to attempt to humanize the mouse immune system in order to address important, human-specific questions that are impossible to study in patients. The successful long-term engraftment of human hemato-lymphoid cells in mice would provide investigators with a relatively inexpensive, small animal model to study clinically-relevant mechanisms as well as facilitate the evaluation of human-specific therapies in vivo. The discovery that targeted mutation of the IL-2 receptor common gamma chain in lymphopenic mice allows for the long-term engraftment of functional human immune cells has advanced greatly our ability to humanize the mouse immune system. The objective of this review is to present a brief overview of the recent advances that have been made in the development and use of humanized mice with special emphasis on autoimmune and chronic inflammatory diseases. In addition, we discuss current challenges and possible solutions for utilizing these unique mouse models to define the human-specific immuno-pathological mechanisms responsible for the induction and perpetuation of chronic gut inflammation.

One of the best characterized mouse models of the inflammatory bowel diseases (IBD; Crohn’s disease, ulcerative colitis) is the CD4(+)CD45RB(high) T cell transfer model of chronic colitis. Following our relocation to Texas Tech University Health Sciences Center (TTUHSC), we observed a dramatic reduction in the incidence of moderate-to-severe colitis from a 16-year historical average of 90% at Louisiana State University Health Sciences Center (LSUHSC) to

Mouse models of disease have been used extensively by the research community for the past three decades to better understand the pathogenesis of different diseases as well as to assess the efficacy and toxicity of different therapeutic agents. Retrospective analyses of numerous preclinical intervention studies using mouse models of acute and chronic inflammatory diseases reveal a generalized failure to translate promising interventions or therapeutics into clinically effective treatments in patients. This is especially true for preclinical investigations using mouse models of the inflammatory bowel diseases (IBD; Crohn’s disease, ulcerative colitis). One potential strategy for improving our ability to discover new therapeutics that may have a reasonable chance of success in clinical trials is to identify the most immunologically-relevant mouse models of human IBD. However, it is becoming increasingly appreciated that the mouse immune system differs substantially from that of humans, and thus, may not express the same pathogenetic mechanisms that are thought to occur in human IBD. This chapter presents a critical evaluation of selected mouse models of IBD and discusses their utility in preclinical studies. In addition, we describe recent advances in generating and utilizing “humanized” mice to study the pathogenesis and treatment of chronic gut inflammation.

The mammalian intestine encounters many more microorganisms than any other tissue in the body thus making it the largest and most complex component of the immune system. Indeed, there are greater than 100 trillion (10(14)) microbes within the healthy human intestine, and the total number of genes derived from this diverse microbiome exceeds that of the entire human genome by at least 100-fold. Our coexistence with the gut microbiota represents a dynamic and mutually beneficial relationship that is thought to be a major determinant of health and disease. Because of the potential for intestinal microorganisms to induce local and/or systemic inflammation, the intestinal immune system has developed a number of immune mechanisms to protect the host from pathogenic infections while limiting the inflammatory tissue injury that accompanies these immune responses. Failure to properly regulate intestinal mucosal immunity is thought to be responsible for the inflammatory tissue injury observed in the inflammatory bowel diseases (IBD; Crohn disease, ulcerative colitis). An accumulating body of experimental and clinical evidence strongly suggests that IBD results from a dysregulated immune response to components of the normal gut flora in genetically susceptible individuals. The objective of this review is to present our current understanding of the role that enteric microbiota play in intestinal homeostasis and pathogenesis of chronic intestinal inflammation.

Hemochromatosis is a highly prevalent genetic disease associated with excessive iron accumulation in a variety of tissues in an age-dependent manner. In a majority of patients (>85%) with hemochromatosis, mutations in the iron-regulatory gene HFE are the cause. Iron, when present in excess, is an inducer of oxidative stress and suppresses mitochondrial function. Patients with hemochromatosis show evidence of colonic inflammation. Further, some studies have shown increased risk for colon cancer associated with genetic mutations known to cause hemochromatosis. Based on these findings in the literature, we hypothesized that hemochromatosis is an important determinant of disease progression in patients with colitis and colon cancer. We tested this hypothesis by comparing progression of experimentally induced colitis and colon cancer between wild type mice and Hfe-null mice, a model for hemochromatosis. We also compared the transcriptome profile between wild type and Hfe-null colonic epithelial cells. In addition, we analyzed fecal bacteria in wild type mice and Hfe-null mice because colonic microbiome is an important determinant of colonic inflammation and colon cancer. With dextran sulfate sodium-induced colitis, Hfe-null mice suffered more weight loss and exhibited more severe bleeding and diarrhea scores than wild type mice. With ApcMin-driven colon and intestinal cancer, Hfe-null mice had more polyps in the small intestine and colon than wild type mice. Transcriptome analysis showed that Hfe-null colonic epithelial cells, compared to wild type cells, had increased expression of the cytokines Ccl3 and Ccl5 and the interferon-stimulated gene 15 (ISG15 or Usp18), which are all known to promote inflammation and cancer. Hfe-null colonic epithelial cells also had decreased expression of Erdr1 (erythroid differentiation regulator 1), whose expression is known to suppress tumor cell proliferation, invasion, migration and metastasis. Analysis of fecal microbiome indicated that the prevalence of Bacteroidetes and Firmicutes decreased while that of Proteobacteria increased in Hfe-null mice compared to wild type mice, a finding particularly striking in male mice. These studies demonstrate that hemochromatosis enhances the progression of colonic inflammation and colon carcinogenesis. This conclusion is further supported by xenograft studies using the colon cancer cell line HCT116 with and without shRNA-induced downregulation of HFE. When HFE was silenced, there was a significant increase in the growth of HCT116 cells in mouse xenografts, demonstrating that inactivation of HFE promotes colon cancer progression. Based on these data, we conclude that the iron-overload disease hemochromatosis is a promoter of disease progression in colitis and colon cancer, and that use of iron chelators might have a logical basis for inclusion in therapeutic modalities in the treatment of colonic inflammation and colon cancer. Citation Format: Vadivel Ganapathy, Ashish Gurav, Jaya P. Gnanaprakasam, Ellappan Babu, Yangzom D. Bhutia, Cynthia Reinoso Webb, Matthew B. Grisham. The iron-overload genetic disease hemochromatosis potentiates colonic inflammation and colon carcinogenesis. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1557. doi:10.1158/1538-7445.AM2015-1557