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Description:
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Coxiella burnetii is an intracellular pathogen that can cause both acute and
chronic disease (Q fever ) in humans and infects many animals with varying clinical
illness and persistence . A guinea pig aerosol -challenge model of acute Q fever was
developed using infection with C . burnetii across a 5 -log range of challenge doses .
Clinical signs included fever , weight loss , respiratory difficulty , and death , with degree
and duration of response corresponding to dose of organism delivered . Histopathologic
evaluation revealed coalescing panleukocytic bronchointerstitial pneumonia 7 days after
a high -dose challenge , resolving to multifocal lymphohistiocytic interstitial pneumonia
by 28 days . Clinical and pathologic changes noted in these guinea pigs were comparable
to those seen in human acute Q fever , making this an accurate and valuable animal
model . This model was used to compare the relative virulence of eight isolates from four
different genotypic groups : I (RSA493 , RSA334 , and RSA270 ) , IV (Q177 and Q173 ) , V
(Q212 and Q217 ) , and VI (5J108 -111 ) . Guinea pigs infected with group I acute -diseaseassociated
isolates had severe respiratory disease , while no to moderate clinical illness
was observed in animals given group IV or V chronic -disease -associated isolates . 5J108 -
111 appeared avirulent . These data suggest that C . burnetii isolates have a range of
disease potentials and support a distinction in strain virulence between established genotypic groups , though isolates within the same genomic group cause similar
pathologic responses . Heterologous protection was confirmed by cross vaccination and
challenge with RSA493 and Q217 . A marked non -specific suppression of
lymphoproliferation was noted at 14 and 28 days post infection with RSA493 ; similar
suppression was seen after infection with Q173 and Q212 but not 5J108 -111 . Proinflammatory
cytokines IFN -γ and TNF -α were produced during early C . burnetii
infection , at which time anti -inflammatory cytokines TGF -β and IL -10 were repressed .
A vaccine made from phase I C . burnetii was found to be completely protective against
lethal infection in the guinea pig model , while vaccination with killed phase II organisms
conferred only partial protection , preventing death and reducing but not precluding fever
and respiratory illness . Protective vaccination significantly stimulated cell -mediated
immunity and elicited increases in IFN -γ , TNF -α , and IL -12p40 mRNA levels . |