An inhalation model of acute Q fever in guinea pigs

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Title: An inhalation model of acute Q fever in guinea pigs
Author: Russell-Lodrigue, Kasi Elizabeth
Abstract: 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 - ? and TNF - ? were produced during early C . burnetii infection , at which time anti -inflammatory cytokines TGF - ? 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 - ? , TNF - ? , and IL -12p40 mRNA levels .
URI: http : / /hdl .handle .net /1969 .1 /ETD -TAMU -1209
Date: 2009-05-15


An inhalation model of acute Q fever in guinea pigs. Available electronically from http : / /hdl .handle .net /1969 .1 /ETD -TAMU -1209 .

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