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PubMed2005

Chronic maternal and fetal Porphyromonas gingivalis exposure during pregnancy in rabbits.

OBJECTIVE: This study was undertaken to develop a rabbit model of maternal exposure to Porphyromonas gingivalis and determine whether fetal or placental exposure occurs. STUDY DESIGN: Subcutaneous steel chambers were implanted in 8 New Zealand White female rabbits. On day 7 of pregnancy, 4 rabbits were inoculated through the chamber with 5 x 10 8 CFU/mL live P gingivalis , and 4 rabbits with broth (controls) and sacrificed at term. Polymerase chain reaction was used to detect P gingivalis in maternal and fetal liver and placenta. Fisher exact test was used to compare P gingivalis detection between groups. RESULTS: Among exposed does, P gingivalis was detected in 33% of the maternal livers, 49% of placentas, and 34% fetal livers compared with none from controls ( P < .001). CONCLUSION: Chronic maternal exposure to P gingivalis results in systemic dissemination, transplacental passage, and fetal exposure. This model may be useful to study placental and fetal effects of this oral pathogen and to study microbial dissemination across the placenta.

Animals↗
PubMed2005

Variation in microbiologic profiles among pregnant women with bacterial vaginosis.

OBJECTIVE: The purpose of this study was to determine if clinical findings and sociodemographic variables among bacterial vaginosis (BV)-positive pregnant women are associated with different microbiologic profiles. STUDY DESIGN: Pregnant women were assessed for BV by Nugent criteria. BV+ women were separated into 6 mutually exclusive microbiologic groups. In unadjusted analyses, we compared (1) sociodemographic and behavioral characteristics, and (2) 3 clinical characteristics among BV+ women with and without Mobiluncus (M+ vs M-). Unadjusted data were analyzed using the chi-square test. Multiple logistic regression was used to assess the likelihood of having clinical signs of BV in women with and without Mobiluncus spp while controlling for confounders. RESULTS: A total of 1756 BV+ pregnant women were followed. The M+ group (n=702) was significantly more likely than the M- group (n=1054) to be non-Hispanic black (80.9% vs 66.2%; P < .0001), older than 21 years (61.7% vs 48.7%; P < .0001), and to have had more than 3 lifetime sexual partners (66.4% vs 54.9%; P < .0001). The M+ group was also more likely to have clue cells on wet mount (63.9% vs 47.2%; P < .0001) and a positive amine odor after addition of KOH (57.2% vs 45.0%; P=.001). There was no difference in other demographic variables or physician diagnosis of abnormal vaginal discharge. In the adjusted analyses for each clinical outcome, all findings were consistent with the unadjusted analyses. CONCLUSION: BV+ pregnant women with Mobiluncus spp are more likely to have clue cells present on wet mount, a positive amine odor after KOH preparation, and to be older, non-Hispanic black, and have had more lifetime sexual partners compared to BV+ women without any Mobiluncus species.

Bacteroidaceae Infections↗
PubMed2005

Insulin-like growth factor and interleukin-1beta levels and subsequent fetal size in response to chronic Porphyromonas gingivalis exposure in the pregnant rabbit.

OBJECTIVE: The purpose of this study was to describe maternal insulin-like growth factor, interleukin-1beta, and fetal size in a rabbit model of Porphyromonas gingivalis exposure. STUDY DESIGN: With the use of a previously described model, 8 New Zealand White rabbits were exposed to either P gingivalis or media during pregnancy and killed at term. Kit and placenta weight were compared between groups. Doe serum insulin-like growth factor system protein and interleukin-1beta levels were compared by analysis of variance for repeated measures; a probability value of <.05 was considered to be significant. RESULTS: No significant differences in kit and placental weights between exposed and unexposed groups were observed. Insulin-like growth factor system proteins increased significantly as pregnancy progressed, but there were no significant differences in insulin-like growth factor system proteins or interleukin-1beta between exposed and unexposed does. CONCLUSION: Chronic P gingivalis exposure does not disrupt insulin-like growth factor system proteins or systemic inflammation and does not impair fetal growth in the pregnant rabbit. Gestational age changes in doe insulin-like growth factor system proteins occur, and the timing of exposure to oral pathogens may influence fetal growth.

Animals↗
PubMed2004

Effect of intrauterine administration of oestradiol on postpartum uterine bacterial infection in cattle.

After parturition fewer first dominant follicles are selected in the ovary ipsilateral to the previously gravid uterine horn in cattle. However, the presence of a large oestradiol-secreting follicle in the ipsilateral ovary is a predictor of fertility, possibly due to a localised effect of oestradiol which increases the rate of elimination of the ubiquitous uterine bacterial contamination that occurs after calving. The present study tested the hypothesis that oestradiol reduces uterine bacterial contamination when administered into the uterine lumen around the expected time for selection of the first postpartum dominant follicle. Animals were infused with saline (n=15) or 10mg oestradiol benzoate (n=15) into the previously gravid uterine horn on Days 7 and 10 postpartum. Peripheral coccygeal blood samples were collected daily and oestradiol concentrations measured by radioimmunoassay (RIA). Uterine lumen swabs were collected 7, 14 and 21 days postpartum for aerobic and anaerobic culture, bacteria were identified and growth scored semi-quantitatively. Plasma oestradiol concentrations were higher for treated animals between Days 7 and 14 (1.4+/-0.1 versus 2.0+/-0.2 pg/ml, P<0.05). Control animals had a similar bacterial growth score on Days 7 and 14, with a lower value on Day 21 (5.7+/-1.0 and 6.1+/-0.7 versus 0.3+/-0.1, P<0.05). However, treated animals had a surprising higher bacterial load on Day 14, than on Days 7 or 21 (7.1+/-0.9 versus 4.0+/-0.6 or 3.6+/-0.6, P<0.05). The increased score was attributable to more pathogens associated with endometritis on Day 14 than Day 7 (5.1+/-1.0 versus 2.5+/-0.5, P<0.05), in particular Prevotella melaninogenicus (1.5+/-0.5 versus 0.7+/-0.2, P<0.05) and Fusobacterium necrophorum (1.5+/-0.4 versus 0.3+/-0.2, P<0.05). In conclusion, administration of oestradiol into the uterine lumen surprisingly increased uterine pathogenic anaerobic bacterial contamination. Thus, it is unlikely that increased fertility associated with a first dominant follicle in the ipsilateral ovary is a consequence of the elimination of bacterial contamination by ovarian oestradiol.

Animals↗
PubMed2006

Paxillin phosphorylation and integrin expression in osteoblasts infected by Porphyromonas gingivalis.

OBJECTIVE: We investigated early biological events initiated by Porphyromonas gingivalis infection of human osteoblasts, focusing on tyrosine-phosphorylation and the expression of key components in focal adhesion and cell signalling. DESIGN: Human primary osteoblasts were challenged for 1h with Porphyromonas gingivalis. Tyrosine-phosphorylation of paxillin and focal adhesion kinase (FAK) was examined by Western blotting. Changes in alpha3- and beta1-integrin mRNA expression were quantified by RT-PCR. RESULTS: Tyrosine-phosphorylation of paxillin was proportional to the size of the Porphyromonas gingivalis inoculum. FAK, a potential kinase for paxillin, was not activated. The amount of alpha3- and beta1-integrins, determined by Western blotting, did not vary significantly, while the corresponding mRNA levels fell significantly when a large bacterial inoculum was used. CONCLUSIONS: These results indicate that Porphyromonas gingivalis infection of osteoblasts in vitro triggers tyrosine-phosphorylation of paxillin but not FAK and modify alpha3- and beta1-integrin mRNA expression. This infection thus appears to have different effects on components with essential roles in focal adhesion (paxillin) and cell signalling (FAK and integrins).

Bacterial Adhesion↗
PubMed2006

Antibacterial activity of a bacteriocin from Lactobacillus paracasei HL32 against Porphyromonas gingivalis.

Porphyromonas gingivalis infections cause problems in periodontal diseases and in certain systemic diseases. There is evidence that Lactobacillus spp. can control populations of P. gingivalis, but there are few data on the effects of purified bacteriocins from Lactobacillus paracasei HL32 on P. gingivalis. The objective of this study was to examine the antibacterial activity of a bacteriocin from L. paracasei HL32 and to relate this activity to its composition. A bacteriocin was purified from culture supernatants of Lactobacillus spp. using a dialysis technique followed by gel-permeation chromatography. Composition of the bacteriocin was characterised by ninhydrin tests, ultraviolet spectrophotometry, thin-layer chromatography, sodium-dodecyl sulphate-polyacrylamide gel electrophoresis, electrospray ionisation mass spectrometry and amino acid analysis. The amino acid sequence from the N-terminal of the bacteriocin was determined. Antibacterial activity was examined by the cylinder plate method, microtitre assay and scanning electron microscopy as compared with standard antibiotics. The bacteriocin had a molecular weight of approximately 56kDa, was comprised of 68% carbohydrate and 32% protein, and showed maximum peak absorbance at 214 and 254nm. The bacteriocin was found to be effective against P. gingivalis; it caused swelling and pore formation on the cell envelope at a minimum bactericidal concentration of 0.14mM, and caused death within 2h. Metronidazole killed P. gingivalis but did not affect the envelope, whereas tetracycline affected P. gingivalis with cell deformation. In conclusion, the bacteriocin from L. paracasei HL32 had the ability to kill P. gingivalis, suggesting that it could be a promising alternative chemotherapeutic agent for P. gingivalis infections.

Amino Acid Sequence↗
PubMed2006

Doxycycline affects diet- and bacteria-associated atherosclerosis in an ApoE heterozygote murine model: cytokine profiling implications.

BACKGROUND: It has been postulated that systemic infection with pathogens such as Porphyromonas gingivalis (Pg) elevates the inflammatory response and increases susceptibility to atherosclerosis. We hypothesized that Doxycycline would be beneficial in diet- and/or Pg-induced atherosclerosis given its role in various cell functions and matrix remodeling. METHODS AND RESULTS: ApoE+/- mice were inoculated weekly with Pg and treated with either Doxycycline or saline; animals were fed either a high-fat or chow diet. Animals were euthanized at 14 or 24 weeks and histomorphometric analysis of atheromatous lesions in proximal aorta, levels of SAA and serum cytokine profiling were performed. Histomorphometric analysis demonstrated that in non-infected mice fed a high fat diet, Doxycycline treatment resulted in a reduction of mean lesions from 10.5%+/-.49 to 1.09%+/-0.102 (p<0.05) at 14 weeks and a reduction from 21.5%+/-6.49 to 8.26%+/-0.162 (p=0.106) at 24 weeks. Chow-fed Pg mice treated with Doxyclycline also resulted in a reduction from 0.62%+/-0.128 to 0.0%+/-0.0 (p<0.05) at 14 weeks and a reduction from 0.92%+/-0.23 to 0.0%+/-0.0 (p<0.05) at 24 weeks. Administration of Doxycycline to mice fed a high fat diet and Pg-inoculated resulted in a reduction of mean percentage of atheromatous lesions from 16.46%+/-1.69 to 1.141%+/-0.23 (p<0.05) at 14 weeks and a reduction from 25.27%+/-1.734 to 0.428%+/-0.033 (p<0.05) at 24 weeks. At this timepoint, SAA levels in Pg-infected animals were reduced by five-fold and three-fold in Doxycycline-treated chow and high fat-diet groups, respectively. Cytokine antibody arrays revealed a marked reduction in the levels of pro-inflammatory cytokines in Doxycycline-treated groups whether Pg-infected or fed a high fat diet while anti-inflammatory cytokines were not affected. Consistent with the role of Doxycycline on matrix proteases, at 24 weeks MMP-9 Serum levels were markedly reduced by 60% (p<0.05) and 30% (p<0.05) with Doxycycline treatment in Pg-infected high fat and chow diet groups, respectively. CONCLUSIONS: Doxycycline decreases pro-inflammatory cytokines and results in reduction of atherosclerosis in ApoE+/-Pg-inoculated and/or high fat diet fed mice.

Animals↗
PubMed2006

Infection with a periodontal pathogen increases mononuclear cell adhesion to human aortic endothelial cells.

BACKGROUND: As a link between periodontal infections and an increased risk for vascular disease has been demonstrated, we assessed the ability of the Gram-negative periodontal pathogen Porphyromonas gingivalis to modulate properties of endothelial cells linked to inflammation and proatherogenic pathways. METHODS AND RESULTS: Primary human aortic endothelial cells (HAEC) were infected with either P. gingivalis strain 381 or its non-invasive fimbriae-deficient mutant, DPG3, and incubated with U-937 monocytes, or Jurkat T cells. P. gingivalis-infected HAEC demonstrated significantly increased adhesion of immune cells compared to non-infected cells or those infected with DPG3. Heat-killed bacteria had no effect on mononuclear cell adhesion and P. gingivalis LPS had only a minimal effect. P. gingivalis infection significantly increased HAEC expression of VCAM-1, ICAM-1 and E-selectin, and enhanced production of IL-6, IL-8 and MCP-1. CONCLUSION: These data demonstrate that live invasive P. gingivalis 381 elicits a pro-atherogenic response in HAEC.

Aorta↗
PubMed2006

Systemic exposure to Porphyromonas gingivalis predicts incident stroke.

Periodontitis has been associated with an increased risk for atherosclerosis. Prospective data concerning its association with risk of stroke, especially those measuring systemic exposure to periodontal pathogens, are scarce. We analyzed if serum antibody levels to two major periodontopathogens predict stroke. The cases and the controls were nested in a random population-based sample of 8911 subjects aged 30-59 years at baseline, who participated in a cardiovascular disease (CVD) risk factor survey in Eastern Finland in 1977 and were followed for 15 years. CVD-free controls (n=516) were matched for sex and 5-year age group with stroke cases (n=470). In subjects free from CVD at baseline (n=893), systemic exposure to Porphyromonas gingivalis increased the risk of stroke: compared to seronegative subjects, men IgA-seropositive and women IgG-seropositive for P. gingivalis had a multivariate odds ratio (OR) (95% CI) of 1.63 (1.06-2.50) and 2.30 (1.39-3.78) for stroke, respectively. Higher OR was observed in males, who had never smoked: compared to seronegative men, P. gingivalis IgA-seropositive men had a multivariate OR of 3.31 (1.31-8.40, p=0.012) for stroke. No association between antibody levels to Actinobacillus actinomycetemcomitans and stroke was found. The results suggest that the systemic exposure to P. gingivalis may predispose to incident stroke.

Adult↗
PubMed2003

Leptin suppresses Porphyromonas gingivalis lipopolysaccharide interference with salivary mucin synthesis.

Leptin, a multifunctional hormone produced predominantly by adipocytes but also identified throughout the glandular tissue of alimentary tract, including salivary glands and oral mucosa, has emerged recently as an important regulator of mucosal inflammatory responses to bacterial infection. In this study, we report that leptin prevents (up to 88.4%) the reduction in mucin synthesis evoked in mucous cells of sublingual salivary gland by LPS of periodontopathic bacterium, Porphyromonas gingivalis. The effect of leptin, moreover, was reflected in a marked decrease in the LPS-induced apoptosis, expression of TNF-alpha, caspase-3 activity, and NO generation. The impedance by leptin of the LPS inhibitory effect on mucin synthesis was blocked by wortmannin, an inhibitor of PI3K, which also obviated the inhibitory effect of leptin on the LPS-induced upregulation in apoptosis, caspase-3 activity, and NO generation. A potentiation in the impedance by leptin of the LPS-induced apoptosis, caspase-3 activity, and NO generation was, however, attained with NOS-2 inhibitor, 1400W, that also caused further enhancement in the impedance by leptin of the LPS detrimental effect on mucin synthesis. Taken together, our data are the first to demonstrate the nature of the involvement of leptin in countering the pathological consequences of P. gingivalis infection on the synthesis of salivary mucins.

Animals↗
PubMed2005

Elevation of galectin-9 as an inflammatory response in the periodontal ligament cells exposed to Porphylomonas gingivalis lipopolysaccharide in vitro and in vivo.

Considerable evidence suggests that periodontal disease not only is caused by bacterial infection but also is associated with host susceptibility. Using in-house cDNA microarray analysis, we attempted to identify gene expression changes in human periodontal ligament (PDL)-derived cells with and without treatment with lipopolysaccharide (LPS) extracted from Porphylomonas gingivalis (P. gingivalis LPS). Of the five up-regulated genes in the PDLs treated with P. gingivalis LPS, galectin-9, which was reported to have eosinophil chemoattraction, was selected for further analyses. By semiquantitative reverse transcriptase-polymerase chain reaction (sqRT-PCR), real-time quantitative RT-PCR, and Western blot analyses, elevated galectin-9 gene expression was detected in LPS-treated PDL-derived cells. Consequently, it was confirmed that the LPS enhances the expression level of galectin-9 mRNA and protein in a time-dependent manner together with interleukin-8. In addition, strong immunoreaction for galectin-9 was detected in the PDL consisting of the periodontal pocket of a patient with severe periodontal disease. Furthermore, significant up-regulation of galectin-9 mRNA expression was detected in the mRNA from PDLs of patients with periodontal disease when compared with healthy donors (P < 0.05). These results suggest that galectin-9 expression is associated with inflammatory reactions in the PDL.

Bacteroidaceae Infections↗
PubMed2005

Inducible nitric oxide synthase mediates bone development and P. gingivalis-induced alveolar bone loss.

The role of inducible nitric oxide synthase (iNOS) in bone development and bacterially induced periodontal bone loss was examined using mice with targeted mutation of the iNOS gene. Femurs of iNOS KO mice showed 30% and 9% higher bone mineral density compared to wild type (WT) at 4 and 9 weeks of age, respectively. Micro-computed tomography revealed that cortical thickness and cortical bone density is increased in the absence of iNOS, while trabecular bone thickness and bone density remains unchanged. Histochemical analysis using TRAP staining showed that osteoclast numbers are lower by 25% in iNOS KO femurs compared to WT femurs. When bone marrow cells were stimulated with M-CSF and RANKL in vitro, iNOS KO cultures developed 51% fewer TRAP-positive multinuclear cells compared to WT cultures. When similar cultures were grown on dentine discs, resorption pit area was decreased by 54% in iNOS KO cultures. Gene expression studies showed that iNOS expression is induced by M-CSF and RANKL in WT bone marrow cultures, while no iNOS transcript was detected in iNOS KO. No compensatory change was detected in the expression of neuronal or endothelial NOS isoforms. There was no difference in RANK and osteoprotegerin expression between iNOS KO and WT bone marrow cultures after M-CSF and RANKL-treatment, while Traf6 expression was significantly lower in the absence of iNOS. In the alveolar bone of the maxilla, the distance between the cementoenamel junction and the alveolar bone crest was larger in iNOS KO compared to WT mice from 6 to 14 weeks of age, indicating a developmental effect of iNOS in oral tissues. Oral administration of the periodontal pathogen Porphyromonas gingivalis caused alveolar bone loss in the maxilla of WT mice, but failed to do so in iNOS KO mice. Expression of the osteoclast marker cathepsin K was 25% lower in iNOS KO alveolar bone. These data indicate that iNOS promotes bone resorption during bone development as well as after bacterial infection, and that iNOS is an important signal for normal osteoclast differentiation.

Alveolar Bone Loss↗
PubMed2006

Preparation and structural determination of large oligosaccharides derived from acharan sulfate.

The structures of a series of large oligosaccharides derived from acharan sulfate were characterized. Acharan sulfate is an unusual glycosaminoglycan isolated from the giant African snail, Achatina fulica. Oligosaccharides from decasaccharide to hexadecasaccharide were enzymatically prepared using heparin lyase II and purified. Capillary electrophoresis and gel electrophoresis confirmed the purity of these oligosaccharides. Their structures, determined by ESI-MS and NMR, were consistent with the major repeating sequence in acharan sulfate, -->4)-alpha-d-GlcN(p)Ac-(1-->4)-alpha-l-IdoA(p)2S-(1-->, terminated by 4-linked alpha-d-GlcN(p)Ac residue at the reducing end and by 4,5-unsaturated pyranosyluronic acid 2-sulfate at the non-reducing end.

Animals↗
PubMed2005

Interleukin-6 negatively regulates Porphyromonas gingivalis fimbria-stimulated fibronectin expression in human gingival fibroblasts.

Our previous study demonstrated that fibronectin (FN) is a negative regulator of Porphyromonas gingivalis fimbria-induced pathogenesis in the initiation and development of chronic periodontal diseases. We show herein the regulatory action of interleukin-6 (IL-6) on FN expression in fimbria-treated human gingival fibroblasts. Interestingly, the decrease in FN expression in the cells treated with fimbriae at a high dose (8 microg of protein ml(-1)) was negated by treatment with anti-IL-6 antibody. Also, the increase in FN expression in cells treated with fimbriae at a low dose (1 microg of protein ml(-1)) was inhibited by exogenous IL-6. These results suggest that P. gingivalis fimbria-stimulated FN expression in human gingival fibroblasts is negatively regulated by endogenous IL-6.

Adult↗
PubMed2005

Mechanisms of Porphyromonas gingivalis-induced monocyte chemoattractant protein-1 expression in endothelial cells.

Monocyte chemoattractant protein-1 (MCP-1) is expressed in vascular endothelial cells of inflamed gingival tissues and plays an important role in periodontal pathogenesis. Endothelial cells produce high levels of MCP-1 in response to Porphyromonas gingivalis, an important periodontal pathogen. The present study investigated the mechanisms involved in MCP-1 production by human umbilical vein endothelial cells (HUVEC) following infection with P. gingivalis. In contrast to P. gingivalis, Bacteroides forsythus only weakly stimulated MCP-1 production while Treponema denticola could not induce MCP-1 in HUVEC. The MCP-1 production was independent of endogenous interleukin (IL)-1alpha as IL-1 receptor antagonist treatment did not reduce MCP-1 production by P. gingivalis. Meanwhile, antioxidant treatment and inhibition of NAD(P)H oxidase significantly reduced MCP-1 production. Pharmacological inhibition of p38 mitogen-associated protein (MAP) kinase, c-Jun N-terminal kinase (JNK), nuclear factor-kappaB (NF-kappaB) or activator protein-1 (AP-1) also substantially attenuated P. gingivalis-induced MCP-1 expression by HUVEC. Indeed, activation of NF-kappaB and AP-1 was observed in P. gingivalis-infected HUVEC. These results suggest that MCP-1 expression is upregulated in P. gingivalis-infected endothelial cells via reactive oxygen species, p38 MAP kinase, JNK, NF-kappaB, and AP-1.

Bacteroidaceae Infections↗
PubMed2006

Periodontopathogenic bacteria multiply in the environmental amoeba Acanthamoeba castellani.

Porphyromonas gingivalis and Prevotella intermedia are obligate anaerobe gram-negative periodontopathogenic bacteria. Free-living amoebae, such as Acanthamoeba spp., are well known as environmental hosts of several human pathogens, such as Franciscella tularensis, Chlamydia pneumoniae, Legionella pneumophila and Mycobacteria spp. This study tested the ability of P. gingivalis and P. intermedia to become internalized, to survive and replicate in Acanthamoeba castellani. Our results show for the first time that P. gingivalis and P. intermedia isolated from periodontitis patients are capable of infecting A. castellani cells in vitro and are able to survive and multiply intracellularly. From our experimental data it can be suggested that periodontopathogenic bacteria might be conditioned in the evolution by amoebae and free-living amoebae can act as an environmental reservoir for these pathogens.

Acanthamoeba castellanii↗
PubMed2006

Construction of a sIgA-enhancing anti-Porphyromonas gingivalis FimA vaccine and nasal immunization in mice.

Porphyromonas gingivalis is implicated in the etiology of chronic periodontitis. Fimbriae are one of several critical surface virulence factors of P. gingivalis. Interleukin 15 (IL-15) is a critical important cytokine for the differentiation of B-1 cells into IgA-inducing cells in mucosal tissues and the proliferation of B cells. The present study constructed a co-expression plasmid pIRES-fimA:IL-15 encoding fimbrinllin (FimA), a subunit of fimbriae and IL-15 as a sIgA-enhancing anti-P. gingivalis FimA vaccine. The plasmid pIRES-fimA:IL-15 was transfected to CHO cells. The expressions of FimA and IL-15 in CHO cells were verified by Western blot and ELISA. Mice were immunized with pIRES-fimA:IL-15 via nasal or intramucusal route. The results showed that nasal immunization was capable of promoting Ag-specific immune responses in the oral region as well as systemic immunity. When immunized via nasal route, IL-15 expressed by the plasmid enhanced FimA-specific sIgA antibody response. In conclusion, a co-expression plasmid pIRES-fimA:IL-15 has been constructed, and when immunized via nasal route, antigen-specific sIgA antibody response could be modulated positively in immunized mice.

Administration, Intranasal↗
PubMed2005

Prevotella bivia necrobacillosis following infectious mononucleosis.

A case of Lemierre's syndrome is reported. Although Fusobacterium species are commonly associated with this presentation, Prevotella bivia was the causative micro-organism identified in this case. The finding that disseminated anaerobic sepsis followed primary EBV infection led to the construction of a hypothetical model of infection.

Adolescent↗