HRMAn 2.0: Next-generation artificial intelligence-driven analysis for broad host-pathogen interactions.

To study the dynamics of infection processes, it is common to manually enumerate imaging-based infection assays. However, manual counting of events from imaging data is biased, error-prone and a laborious task. We recently presented HRMAn (Host Response to Microbe Analysis), an automated image analysis program using state-of-the-art machine learning and artificial intelligence algorithms to analyse pathogen growth and host defence behaviour. With HRMAn, we can quantify intracellular infection by pathogens such as Toxoplasma gondii and Salmonella in a variety of cell types in an unbiased and highly reproducible manner, measuring multiple parameters including pathogen growth, pathogen killing and activation of host cell defences. Since HRMAn is based on the KNIME Analytics platform, it can easily be adapted to work with other pathogens and produce more readouts from quantitative imaging data. Here we showcase improvements to HRMAn resulting in the release of HRMAn 2.0 and new applications of HRMAn 2.0 for the analysis of host-pathogen interactions using the established pathogen T. gondii and further extend it for use with the bacterial pathogen Chlamydia trachomatis and the fungal pathogen Cryptococcus neoformans.

Effect of coexistence of Chlamydia pneumoniae and increased epicardial fat thickness on coronary artery disease.

OBJECTIVE: Epicardial fat thickness (EFT) and chlamydia infection are independent cardiovascular risk factors in coronary artery disease (CAD). We aimed to evaluate the effect of coexistence of EFT and chlamydia infection on the presence and severity of CAD in patients with stable angina pectoris (SAP). PATIENTS AND METHODS: The study included 208 patients with SAP, divided into a CAD group (n=112) and a control group (n=96). The presence of Chlamydia pneumoniae-IgG (CP-IgG), EFT, and left ventricular ejection fraction (LVEF) were compared between groups. RESULTS: CP-IgG, LVEF, and EFT were found to be independent predictors of CAD (CP-IgG, OR=1.559, p=0.021; LVEF, OR=0.798, p<0.001; EFT, OR=3.175, p=0.026). Moreover, a statistically significant interaction was detected between CP-IgG and EFT for predicting the presence of CAD (p<0.001). A good positive correlation was found between EFT and Gensini score (r=0.684, p<0.001). CONCLUSIONS: We found that there was an interaction between CP-Ig and EFT for CAD development. This finding suggests that the interaction of CP-IgG and EFT plays a prominent role in the inflammatory process.

Chlamydia abortus in Pregnant Woman with Acute Respiratory Distress Syndrome.

We describe a case of Chlamydia abortus in a woman in rural France who was pregnant, developed severe generalized infection, and suffered fetal loss. The case stresses the need for healthcare personnel to perform thorough anamnesis in pregnant women in farming areas and to advise them to avoid contact with small ruminants.

Elderly Fitz-Hugh-Curtis syndrome observed with superb microvascular imaging system.

Fitz-Hugh-Curtis syndrome (FHCS) is defined as inflammation on the surface of the liver following sexually transmitted chlamydia infection. We successfully observed the microvascular structure of the inflamed portion between the abdominal wall and surface of the liver in an elderly patient with FHCS using a superb microvascular imaging (SMI) system, a new technology developed for observing minute vascular flow. An 80-year-old Japanese female with right dorsal to lateral abdominal pain and fever came to our hospital. Anti-chlamydia antibodies were positive. SMI revealed signals suggesting small vessels passing from the liver surface to the hypoechoic space.

Fitz-Hugh-Curtis Syndrome Consequent to a Wound Infection Following Removal of a Peritoneal Dialysis Catheter.

Fitz-Hugh-Curtis syndrome (FHCS) is a condition characterized by inflammation of the liver capsule (perihepatitis) and adjacent peritoneal surfaces. We report a case of FHCS developing in a peritoneal dialysis (PD) patient in whom catheter removal due to recurrent peritonitis was complicated by post-operative wound infection. To the best of our knowledge, this is the first case description of FHCS in the context of PD.

MRI as a Novel In Vivo Approach for Assessing Structural Changes of Chlamydia Pathology in a Mouse Model.

Chlamydia trachomatis is among the most prevalent of sexually transmitted diseases. While Chlamydia infection is a reportable event and screening has increased over time, enhanced surveillance has not resulted in a reduction in the rate of infections, and Chlamydia infections frequently recur. The development of a preventative vaccine for Chlamydia may be the only effective approach for reducing infection and the frequency of pathological outcomes. Current vaccine research efforts involve time consuming and/or invasive approaches for assessment of disease state, and MRI presents a clinically translatable method for assessing infection and related pathology both quickly and non-invasively. Longitudinal T2-weighted MRI was performed over 63 days on both control or Chlamydia muridarum challenged mice, either with or without elementary body (EB) immunization, and gross necropsy was performed on day 65. A scoring system was developed to assess the number of regions affected by Chlamydia pathology and was used to document pathology over time and at necropsy. The scoring system documented increasing incidence of pathology in the unimmunized and challenged mice (significantly greater compared to the control and EB immunized-challenged groups) by 21 days post-challenge. No differences between the unchallenged and EB immunized-challenged mice were observed. MRI scores at Day 63 were consistently higher than gross necropsy scores at Day 65, although two of the three groups of mice showed no significant differences between the two techniques. In this work we describe the application of MRI in mice for the potential evaluation of disease pathology and sequelae caused by C. muridarum infection and this technique's potential for evaluation of vaccines for Chlamydia.

Post-vaccination MDEM associated with MOG antibody in a subclinical Chlamydia infected boy.

The mechanism of post-vaccination acute disseminated encephalomyelitis (ADEM) has been hypothesized as resulting from vaccination-injected antigens cross-reacting with myelin components, however, a precise etiology has been uncertain. In this report, we describe the case of a 6-year-old Japanese boy who had multiphasic disseminated encephalomyelitis (MDEM), and was positive for both anti-myelin oligodendrocyte glycoprotein (MOG) antibodies and Chlamydophila pneumoniae antibodies. After vaccinations that were the second one for measles and rubella, and the booster immunization for Japanese encephalitis, the patient presented with fever, headache, vomiting, and a change in personality. He was treated with a high-dose of intravenous methylprednisolone in the diagnosis of ADEM. However, these symptoms recurred with different magnetic resonance imaging lesion, and he was diagnosed as MDEM. Retrospective testing for pathogens revealed C. pneumoniae IgM and IgG antibodies, and it was considered that he was infected with C. pneumoniae subclinically. The patient's serum indicated a positive response for the anti-MOG antibody from the onset of the ADEM diagnosis and in all recurrent episodes. Chlamydia species infection has been known to play a role in demyelinating diseases. It is also known that the anti-MOG antibody may be present but not exhibit its pathogenesis in the absence of a cell-mediated inflammatory response; however, the precise mechanism of action of the anti-MOG antibodies is not yet determined. We propose the possibility that post-vaccination demyelinating disease may result from the synergistic effects of a preceding anti-MOG antibody, possibly produced in response to a subclinical Chlamydia species infection.

Does the Degree of Perihepatitis Have Any Relevance to the Severity of the Manifestations of Pelvic Inflammatory Disease on Multidetector Computed Tomography?

PURPOSE: This study aimed to evaluate the relationship between the degree of perihepatitis and the severity of pelvic inflammatory disease (PID) on multidetector computed tomography (MDCT). METHODS: A total of 177 women with PID who underwent biphasic abdominal computed tomography (CT) scans were enrolled. Two reviewers retrospectively reviewed the CT scans with consensus and subjectively categorized the severity of PID into 4 grades (normal, mild, moderate, and severe). Another reviewer independently assigned the extent (grades 0 to 4) and the depth (grades 0 to 4) of hepatic surface enhancement in terms of the degree of perihepatitis. Relationships between the degree of perihepatitis and the CT severity as well as each CT manifestation of PID were evaluated using the χ test or a cumulative logistic regression analysis. RESULTS: Of the 177 patients, 99 (55.9%) showed hepatic surface enhancement. The severity of PID on MDCT was significantly related with the degree of perihepatitis (all P < 0.001). Salpingitis, oophoritis, pelvic fat haziness, complicated ascites, and omental/mesenteric fat infiltration were significantly related with the degree of perihepatitis (all P < 0.05). Among these variables, omental/mesenteric fat infiltration (odds ratio = 10.9) and salpingitis (odds ratio = 6.0) were the CT manifestations that were most associated with the presence of perihepatitis in PID. CONCLUSIONS: The degree of perihepatitis seems to show a relationship with the severity of PID on MDCT. Omental/mesenteric fat infiltration and salpingitis can be strongly related with perihepatitis in PID.

Validation of ultrasonography in detecting structural disease of the urogenital tract of the koala, Phascolarctos cinereus.

A retrospective review of case records of ultrasonography and necropsy outcomes of 62 koalas was used to investigate the accuracy of ultrasonography in assessing koala urogenital tract structural disease at the Port Macquarie Koala Hospital. The results showed high concordance, supporting ultrasonography as an effective tool for evaluating structural disease of the koala urogenital tract, most commonly seen with chlamydiosis. The study also illustrates the advances benefiting animal welfare that can be made by wildlife carer groups through using a scientific, evidence-based approach.

Usefulness of 11C-choline positron emission tomography for genital chlamydial infection assessment in a BALB/c murine model.

PURPOSE: The aim of this study is to explore the feasibility of 11C-Choline PET in the assessment of the degree of inflammation in the Chlamydia muridarum genital infection model. PROCEDURES: Forty female Balb/c mice received 2.5 mg of medroxyprogesterone acetate i.m. 9 and 2 days prior to the infection: 21 mice were infected by C. muridarum into the vaginal vault, 12 mice were treated with inactivated chlamydiae, and 7 mice were SPG buffer-treated as negative controls. Three healthy control mice were not treated with progesterone. Mice in each category were randomly subdivided in two groups: (1) sacrificed at 5, 10, 15, and 20 days for histological analysis and (2) undergoing 11C-Choline PET at days 5, 10, and 20 post-infection (20 MBq of 11C-Choline, uptake time of 10 min, acquisition through a small-animal PET tomograph for 15 min). RESULTS: Infected animals showed a significantly higher standardized uptake value than both controls and animals inoculated with heat-inactivated chlamydiae in each PET scan (P<0.05). All organs of the infected animals had scores of inflammation ranging between 2 and 3 at day 5, decreasing to 1-2 at day 20. CONCLUSIONS: This preliminary result demonstrated that 11C-Choline PET can highlight a specific proliferation mechanism of inflammatory cells induced by C. muridarum, thanks to a very high sensitivity in detecting very small amounts of tracer in inflammatory cells.