Application of Sartwell's Model (Lognormal Distribution of Incubation Periods) to Age at Onset and Age at Death of Foals with <i>Rhodococcus equi</i> Pneumonia as Evidence of Perinatal Infection

Horowitz, Miriam L.; Cohen, Noah D.; Takaı̈, Shinji; Becu, Teotimu; Chaffin, M. Keith; Chu, Karin K.; Magdesian, K. Gary; Martens, Ronald J.

doi:10.1111/j.1939-1676.2001.tb02307.x

Cited by 28 publications

(7 citation statements)

References 17 publications

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“…Although CTB is an adjuvant known to induce IgA responses at mucosal surfaces [59], we nonetheless observed a significantly higher proportion of foals from the EBRE2 group with increased R. equi -specific nasal IgA compared to the saline control group. We observed that both total and R. equi -specific nasal IgA amounts increased significantly with age, consistent with what has been reported previously for total IgA [49]; to our knowledge, this is the first such report for R. equi -specific nasal IgA. These findings indicate nasal mucosal immunity against R. equi may be relatively diminished in newborn foals, possibly rendering them more susceptible infection.…”

Section: Discussionsupporting

confidence: 92%

“…We chose to evaluate immune responses during the first month of life on the basis of evidence that natural infection with R. equi generally occurs early in life [48], [49]. We elected to use ratios (day 32 values relative to day 2) because of considerable variation in absolute values among individual foals and between ages (e.g., declining total antibody concentrations or increasing IFN-γ production with age).…”

Section: Discussionmentioning

confidence: 99%

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Immunogenicity of an Electron Beam Inactivated Rhodococcus equi Vaccine in Neonatal Foals

et al. 2014

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Rhodococcus equi is an important pathogen of foals that causes severe pneumonia. To date, there is no licensed vaccine effective against R. equi pneumonia of foals. The objectives of our study were to develop an electron beam (eBeam) inactivated vaccine against R. equi and evaluate its immunogenicity. A dose of eBeam irradiation that inactivated replication of R. equi while maintaining outer cell wall integrity was identified. Enteral administration of eBeam inactivated R. equi increased interferon-γ production by peripheral blood mononuclear cells in response to stimulation with virulent R. equi and generated naso-pharyngeal R. equi-specific IgA in newborn foals. Our results indicate that eBeam irradiated R. equi administered enterally produce cell-mediated and upper respiratory mucosal immune responses, in the face of passively transferred maternal antibodies, similar to those produced in response to enteral administration of live organisms (a strategy which previously has been documented to protect foals against intrabronchial infection with virulent R. equi). No evidence of adverse effects was noted among vaccinated foals.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Immunogenicity of an Electron Beam Inactivated Rhodococcus equi Vaccine in Neonatal Foals

et al. 2014

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“…The lack of an effective vaccine is likely attributable to the complexity of immunity to R. equi [7]–[9], and the finding that foals appear to be infected very early in life [10], [11], when immune responses are naïve or deficient. It is generally accepted that a vaccine must be able to provide foals with protection against infection with R. equi during early life [5].…”

Section: Introductionmentioning

confidence: 99%

Effects of Administration of Live or Inactivated Virulent Rhodococccus equi and Age on the Fecal Microbiome of Neonatal Foals

et al. 2013

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Background Rhodococcus equi is an important pathogen of foals. Enteral administration of live, virulent R. equi during early life has been documented to protect against subsequent intrabronchial challenge with R. equi, indicating that enteral mucosal immunization may be protective. Evidence exists that mucosal immune responses develop against both live and inactivated micro-organisms. The extent to which live or inactivated R. equi might alter the intestinal microbiome of foals is unknown. This is an important question because the intestinal microbiome of neonates of other species is known to change over time and to influence host development. To our knowledge, changes in the intestinal microbiome of foals during early life have not been reported. Thus, the purpose of this study was to determine whether age (during the first month of life) or administration of either live virulent R. equi (at a dose reported to protect foals against subsequent intrabronchial challenge, viz., 1×1010 colony forming units [CFU]) or inactivated virulent R. equi (at higher doses, viz., 2×1010 and 1×1011 [CFU]) altered the fecal microbiome of foals.Methodology/Principal FindingsFecal swab samples from 42 healthy foals after vaccination with low-dose inactivated R. equi (n = 9), high-dose inactivated R. equi (n = 10), live R. equi (n = 6), control with cholera toxin B (CTB, n = 9), and control without CTB (n = 8) were evaluated by 454-pyrosequencing of the 16S rRNA gene and by qPCR. No impact of treatment was observed among vaccinated foals; however, marked and significant differences in microbial communities and diversity were observed between foals at 30 days of age relative to 2 days of age.ConclusionsThe results suggest age-related changes in the fecal microbial population of healthy foals do occur, however, mucosal vaccination does not result in major changes of the fecal microbiome in foals.

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“…The relatively reduced/repressed expression of such genes could also reflect immune-modulation of host responses by the pathogen for its survival. If foals generally become infected early in life, as supported by some research findings [7], [8], the genes and associated pathways identified by this study could be targeted for disease prevention or for developing novel therapeutic interventions. For example, enhanced MHC II/Th1-type immune responses might help protect foals against R. equi and other intracellular pathogens (e.g., Salmonella ) during early life.…”

Section: Discussionmentioning

confidence: 53%

“…The finding that R. equi pneumonia is essentially restricted to foals is likely related to exposure and infection during early life and naïve or diminished immune responses of neonatal foals. Although the age at which foals develop R. equi pneumonia remains unknown, epidemiological and clinical evidence indicate that foals are likely infected very early in life [7], [8]. This evidence is consistent with the insidious development of clinical signs in most affected foals [5], and the time required for development of large, pyogranulomatous lesions caused by R. equi .…”

Section: Introductionmentioning

confidence: 55%

Age-Related Changes following In Vitro Stimulation with Rhodococcus equi of Peripheral Blood Leukocytes from Neonatal Foals

et al. 2013

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Rhodococcus equi is an intracellular bacterium primarily known as an equine pathogen that infects young foals causing a pyogranulomatuous pneumonia. The molecular mechanisms mediating the immune response of foals to R. equi are not fully elucidated. Hence, global genomic high-throughput tools like gene expression microarrays might identify age-related gene expression signatures and molecular pathways that contribute to the immune mechanisms underlying the inherent susceptibility of foals to disease caused by R. equi. The objectives of this study were 2-fold: 1) to compare the expression profiles at specific ages of blood leukocytes from foals stimulated with virulent R. equi with those of unstimulated leukocytes; and, 2) to characterize the age-related changes in the gene expression profile associated with blood leukocytes in response to stimulation with virulent R. equi. Peripheral blood leukocytes were obtained from 6 foals within 24 hours (h) of birth (day 1) and 2, 4, and 8 weeks after birth. The samples were split, such that half were stimulated with live virulent R. equi, and the other half served as unstimulated control. RNA was extracted and the generated cDNA was labeled with fluorescent dyes for microarray hybridizations using an equine microarray. Our findings suggest that there is age-related differential expression of genes involved in host immune response and immunity. We found induction of genes critical for host immunity against pathogens (MHC class II) only at the later time-points (compared to birth). While it appears that foals up to 8-weeks of age are able to initiate a protective inflammatory response against the bacteria, relatively decreased expression of various other immune-related genes points toward inherent diminished immune responses closer to birth. These genes and pathways may contribute to disease susceptibility in foals if infected early in life, and might thus be targeted for developing preventative or therapeutic strategies.

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Application of Sartwell's Model (Lognormal Distribution of Incubation Periods) to Age at Onset and Age at Death of Foals with Rhodococcus equi Pneumonia as Evidence of Perinatal Infection

Cited by 28 publications

References 17 publications

Immunogenicity of an Electron Beam Inactivated Rhodococcus equi Vaccine in Neonatal Foals

Immunogenicity of an Electron Beam Inactivated Rhodococcus equi Vaccine in Neonatal Foals

Effects of Administration of Live or Inactivated Virulent Rhodococccus equi and Age on the Fecal Microbiome of Neonatal Foals

Age-Related Changes following In Vitro Stimulation with Rhodococcus equi of Peripheral Blood Leukocytes from Neonatal Foals

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