Experimental congenital syphilis: guinea pig model

Wicher, Konrad; Baughn, Robert E.; Wicher, Victoria; Nakeeb, Shaheen

doi:10.1128/iai.60.1.271-277.1992

Cited by 17 publications

(10 citation statements)

References 29 publications

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“…The C4-deficient (C4D) guinea pig strain, genetically related to inbred strain 13, is very susceptible (50% infective dose ϭ 10 2 organisms), whereas the Albany (Alb) line, which is haplotype identical to inbred strain 2, is highly resistant (50% infective dose, Ͼ10 9 organisms) to cutaneous infection by T. pallidum (37,38). The genetic backgrounds and clinical and immunological responses of these two partially inbred strains compared with those of inbred strains 2 and 13 have been previously reported (34,35,37). It should be stressed that C4D animals have a health status, life span, humoral and cellular immunocompetence, and susceptibilities to infectious agents similar to those of the original, complement-sufficient strain 13 (5).…”

Section: Methodsmentioning

confidence: 99%

“…Most adult experimental and control animals were sacrificed, and their organs were tested by PCR after 2 to 5 months of infection, representing the latent stage of syphilis in the animal model (Table 1). To assess the presence of T. pallidum DNA in the organs of serologically positive (immunoglobulin M [IgM]) neonates (34,39), pups born to i.d.-infected C4D dams were sacrificed during the first week of life. Organs from pups born to HKTP-injected Alb mothers were collected at 1 to 2 months of age, as it was very unlikely that dead organisms could cross the maternal placenta, much less persist in the progeny for a longer period.…”

Section: Methodsmentioning

confidence: 99%

“…(i) Treponemal antibodies. Treponemal antibodies of the IgM and IgG isotypes were examined by enzyme-linked immunosorbent assay (ELISA), as previously reported (34). We used microplates coated with Percoll-purified 10% alcohol-fixed T. pallidum organisms as described by Zeltzer et al (40).…”

Section: Methodsmentioning

confidence: 99%

“…In the present study, we attempted to fill this gap in information by using PCR, one of the most sensitive and specific tests available for the detection of T. pallidum in tissues and body fluids (6,29,35). We took advantage of the availability of two strains of guinea pigs which as adults show opposite susceptibilities to cutaneous infection by T. pallidum (38) and the lack of obvious clinical signs of infection in serologically reactive, congenitally infected offspring of both strains (34).…”

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confidence: 99%

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Target organs of infection in guinea pigs with acquired congenital syphilis

et al. 1996

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The target organs of infection in guinea pigs with asymptomatic acquired or congenital syphilis were identified by PCR and in some cases by rabbit infectivity test (RIT). The prevalence of Treponema pallidum DNA was examined in the following seven organs: the inguinal and mesenteric lymph nodes, spleen, liver, kidney, heart, and brain. Test samples consisted of 95 organs from two genetically different strains of female guinea pigs (C4-deficient and Albany) with different susceptibilities to cutaneous infection by T. pallidum and 195 organs from their asymptomatic offspring. Twenty organs from dams of both strains injected with heat-killed T. pallidum and 19 organs from their progeny served as negative controls. The infections of mothers and neonates were documented by PCR, RIT, and serology. Though any of the organs tested could be infected, there was a spirochetal predilection for some anatomical locations, such as the lymph nodes, heart, and brain, regardless of the strain, route of maternal infection, and age. None of the 49 organs collected from control animals were positive by PCR. In infected C4-deficient dams, one to four organs were positive by PCR, whereas the organs of 7 of their 27 (25%) asymptomatic offspring were treponemal DNA negative, despite evidence of immunoglobulin M treponemal antibodies. Comparative analysis done by both PCR and RIT on a limited number of samples showed 90% agreement between results. An examination of multiple samples obtained from single organs demonstrated that even within 24 h of spirochetemia, when most organs appeared to be infected, not all samples from an individual organ were positive by PCR. A specific immunological response in guinea pigs with congenital syphilis was a more consistent parameter of vertical transmission than was an analysis of T. pallidum DNA.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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Target organs of infection in guinea pigs with acquired congenital syphilis

et al. 1996

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“…70 days) make these animals an appropriate model for congenital syphilis. We are presently exploring the production of immune complexes and rheumatoid factor in C4D neonates born to syphilitic mothers (23). This phenomenon has been observed in human congenital syphilis (discussed in reference 1), but its mechanism is unknown.…”

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confidence: 94%

Median infective dose of Treponema pallidum determined in a highly susceptible guinea pig strain

Wicher

1991

Infect Immun

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The median infective dose of Treponema pallidum subsp. paUidum and the production of immunity to reinfection in C4D guinea pigs have been determined with 10' to 106 organisms per infective dose. The mean infective dose is 102 organisms, and immunity-in those animals that demonstrated lesions-developed after 4.5 months postinfection. The suitability of the guinea pig as an alternative model for venereal syphilis has been gradually established (11, 19). We have examined inbred strains 2 and 13, outbred strains Hartley and Albany, and a strain deficient in the fourth complement component (C4D). We have found that the C4D animals are the most susceptible to Treponema pallidum infection and develop the most severe clinical symptoms among the various strains of guinea pigs (21). Possibly because of their high susceptibility, the clinical course of T. pallidum infection in C4D animals is practically unaffected by the factors of age, sex, and site of inoculation (22). Moreover, like humans, rabbits, or inbred strain 2 guinea pigs, T. pallidum-infected C4D animals respond with production of circulating immune complexes and autoantibodies to fibronectin and creatine kinase (2). Although C4D is not strictly an inbred strain, we have demonstrated that differences in histocompatibility within the strain seem to be negligible, as indicated by mixed lymphocyte cultures and prolonged (at least up to 6 months posttransfusion) survival of cells adoptively transferred (24). This is consistent with the concept that graft-versus-host reaction is very mild or unnoticeable in guinea pigs (14). Webster et al. (15) reported the establishment of a successful allogeneic chimeric state in C4D guinea pigs (Hartley-C4D) for more than 1 year. The C4D guinea pig has also a great potential for experimental congenital syphilis (23) and for establishing a guinea pigadapted strain of T. pallidum (20). The potential usefulness of the C4D guinea pig for experimental syphilis calls for determination of the median infective dose (ID50) of T.

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