Haemophilus influenzae Meningitis in Infant Rats after Intranasal Inoculation

Moxon, E. Richard; Smith, Arnold L.; Averill, Damon R.; Smith, David H.

doi:10.1093/infdis/129.2.154

Cited by 235 publications

(127 citation statements)

References 22 publications

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“…injiuenzae type b infections, until the introduction of the infant rat model (Moxon et al, 1974). This has been shown to reflect faithfully much of what happens in human infections with this organism.…”

Section: Bacteraemic Infectionsmentioning

confidence: 76%

The pathogenicity of Haemophilus influenzae

Turk

1984

Journal of Medical Microbiology

310

147

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Problems about the pathogenicity of an organism can be classified as: (1) clinical and epidemiological-what diseases does it cause or take part in, and when? (2) research (with prophylactic and therapeutic implications)-how does it do so? Category (1) answers for Haemophilus injuenzae began in 1892, with Pfeiffer's claim that it was the cause of influenza; but the true picture of the range of pathogenic activities of this species became clear in the period 1930-1960 answers have in general been more recent, and are still far from complete (as is the case with most pathogens); but a fascinating array of contributions has appeared in the past few years. What and when?To discuss the pathogenicity of H . injuenzae as though the species were in this respect a single entity would be to confuse things that differ widely. It has been clear for over 50 years (Pittman, 1931), but not known as widely as it should have been, that a minority of H. injluenzae strains have polysaccharide capsules, and that one of the six capsular types (type b) differs in pathogenicity from the rest of the species at least as markedly as do streptococci of Lancefield's group A from other P-haemolytic streptococci. The main facts about the distribution and pathogenicity of capsulated and non-capsulated strains of H. injluenzae are summarised in the table. The species has 00 non-human hosts. Capsular type bThe 2 4 % carriage rates for H. injluenzae type b listed in the table represent the findings of numerous surveys, each of which was a "snapshot" of the distribution of the organism in one community at one time. These give no information about the dynamics of carriage. Rates in the range 2 4 % would be found, for example, in a community of which each member carried the organism for about 2 months during a 5-year period. There is some evidence (e.g., Turk, 1963) that the duration of carriage of H. injluenzae type b by individual children is often of that order. Moreover, when Sell, Turner and Federspiel(l973) studied 55 children through their first 5 years of life, culturing nasopharyngeal swabs mostly at 3-month intervals, they isolated H.

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Section: Bacteraemic Infectionsmentioning

confidence: 76%

The pathogenicity of Haemophilus influenzae

Turk

1984

Journal of Medical Microbiology

310

147

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“…influenzae is an uncommon but sometimes devastating cause of human endophthalmitis that frequently results in blindness (2). In infant rats, H. influenzae serotype b strains of independent origin are reported to cause endogenous endophthalmitis (46,50,61) that appears to stem from hematogenous seeding (50). Endophthalmitis was observed as a late clinical finding associated with systemic infection of infant rats by strain HI689.…”

Section: Resultsmentioning

confidence: 99%

Complex Role of Hemoglobin and Hemoglobin-Haptoglobin Binding Proteins in Haemophilus influenzae Virulence in the Infant Rat Model of Invasive Infection

Seale¹,

Morton²,

Whitby³

et al. 2006

Infect Immun

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Haemophilus influenzae requires an exogenous heme source for aerobic growth in vitro. Hemoglobin or hemoglobin-haptoglobin satisfies this requirement. Heme acquisition from hemoglobin-haptoglobin is mediated by proteins encoded by hgp genes. Both Hgps and additional proteins, including those encoded by the hxu operon, provide independent pathways for hemoglobin utilization. Recently we showed that deletion of the set of three hgp genes from a nontypeable strain (86-028NP) of H. influenzae attenuated virulence in the chinchilla otitis media model of noninvasive disease. The present study was undertaken to investigate the role of the hgp genes in virulence of the wild-type serotype b clinical isolate HI689 in the infant rat model of hematogenous meningitis, an established model of invasive disease requiring aerobic growth. Bacteremia of high titer and long duration (>14 days) and histopathologically confirmed meningitis occurred in >95% of infant rats challenged at 5 days of age with strain HI689. While mutations disrupting either the Hgp-or Hxu-mediated pathway of heme acquisition had no effect on virulence in infant rats, an isogenic mutant deficient for both pathways was unable to sustain bacteremia or produce meningitis. In contrast, mutations disrupting either pathway decreased the limited ability of H. influenzae to initiate and sustain bacteremia in weanling rats. Biochemical and growth studies also indicated that infant rat plasma contains multiple heme sources that change with age. Taken together, these data indicate that both the hgp genes and the hxuC gene are virulence determinants in the rat model of human invasive disease.

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“…Thus, the portal of entry of the relevant pathogen should reflect that of the natural human infection and reproducibly give rise to similar pathology of sufficient duration to allow for therapeutic intervention. The techniques used should not limit the applicability of the procedure and should not contribute to disease outcome 20 . The model of H. influenzae meningitis in infant rats developed by Moxon and colleagues satisfies these criteria 20 ; the natural infection occurs after colonization of the mucosal membranes of the upper respiratory tract and this important feature was replicated in the rat pups by non-traumatic instillation of the bacteria onto the membranes of the nasal passages.…”

Section: Discussionmentioning

confidence: 99%

“…The techniques used should not limit the applicability of the procedure and should not contribute to disease outcome 20 . The model of H. influenzae meningitis in infant rats developed by Moxon and colleagues satisfies these criteria 20 ; the natural infection occurs after colonization of the mucosal membranes of the upper respiratory tract and this important feature was replicated in the rat pups by non-traumatic instillation of the bacteria onto the membranes of the nasal passages. Importantly, the age-dependent nature of the infection was replicated in the model.…”

Section: Discussionmentioning

confidence: 99%

Non-Invasive Model of Neuropathogenic <em>Escherichia coli</em> Infection in the Neonatal Rat

Dalgakiran

Witcomb

McCarthy

et al. 2014

JoVE

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Investigation of the interactions between animal host and bacterial pathogen is only meaningful if the infection model employed replicates the principal features of the natural infection. This protocol describes procedures for the establishment and evaluation of systemic infection due to neuropathogenic Escherichia coli K1 in the neonatal rat. Colonization of the gastrointestinal tract leads to dissemination of the pathogen along the gut-lymph-blood-brain course of infection and the model displays strong age dependency. A strain of E. coli O18:K1 with enhanced virulence for the neonatal rat produces exceptionally high rates of colonization, translocation to the blood compartment and invasion of the meninges following transit through the choroid plexus. As in the human host, penetration of the central nervous system is accompanied by local inflammation and an invariably lethal outcome. The model is of proven utility for studies of the mechanism of pathogenesis, for evaluation of therapeutic interventions and for assessment of bacterial virulence.

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Haemophilus influenzae Meningitis in Infant Rats after Intranasal Inoculation

Cited by 235 publications

References 22 publications

The pathogenicity of Haemophilus influenzae

The pathogenicity of Haemophilus influenzae

Complex Role of Hemoglobin and Hemoglobin-Haptoglobin Binding Proteins in Haemophilus influenzae Virulence in the Infant Rat Model of Invasive Infection

Non-Invasive Model of Neuropathogenic <em>Escherichia coli</em> Infection in the Neonatal Rat

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