An Intriguing Case of Multisystem Inflammatory Syndrome in an Adult Patient with Remote Infection with COVID-19 and Acute Chlamydia

Introduction. COVID-19 is associated with a broad range of immune inflammatory phenomena, with different manifestations in adults and children. We describe a case of COVID-19-related multisystem inflammatory syndrome in an adult (MIS-A), similar to that described in children (MIS-C), which may have been set off by an unrelated secondary infection. Case. A 27-year-old male patient presented with acute epididymitis secondary to acute Chlamydia infection that progressed to multisystem inflammatory failure with respiratory failure requiring endotracheal intubation and mechanical ventilation, cardiogenic shock with heart failure, and gastrointestinal and renal dysfunction. He tested negative for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by reverse transcriptase-polymerase chain reaction on a nasopharyngeal swab thrice within 4 days of presentation, but positive for SARS-CoV-2 immunoglobulin G antibody signifying remote infection. The patient was treated with tocilizumab and steroids, along with doxycycline for concurrent Chlamydia infection, resulting in dramatic improvement in all organ function. We suspect that C. trachomatis infection in this instance may have triggered an aberrant immune response that was shaped by prior exposure to SARS-CoV-2. Conclusion. We present a case of an adult patient with acute Chlamydia trachomatis infection occurring in the wake of asymptomatic (or at least unrecognized) COVID-19 resulting in MIS-A. Clinicians should be alert to the possibility of other such unusual reactions occurring in the aftermath of COVID-19. This case also highlights the importance for clinicians who care for adult patients of being familiar with the multisystem inflammatory syndrome of children, as an identical syndrome may occur in adult patients.

Multidimensional analysis of immune responses identified biomarkers of recent Mycobacterium tuberculosis infection

The risk of tuberculosis (TB) disease is higher in individuals with recent Mycobacterium tuberculosis (M.tb) infection compared to individuals with more remote, established infection. We aimed to define blood-based biomarkers to distinguish between recent and remote infection, which would allow targeting of recently infected individuals for preventive TB treatment. We hypothesized that integration of multiple immune measurements would outperform the diagnostic performance of a single biomarker. Analysis was performed on different components of the immune system, including adaptive and innate responses to mycobacteria, measured on recently and remotely M.tb infected adolescents. The datasets were standardized using variance stabilizing scaling and missing values were imputed using a multiple factor analysis-based approach. For data integration, we compared the performance of a Multiple Tuning Parameter Elastic Net (MTP-EN) to a standard EN model, which was built to the individual adaptive and innate datasets. Biomarkers with non-zero coefficients from the optimal single data EN models were then isolated to build logistic regression models. A decision tree and random forest model were used for statistical confirmation. We found no difference in the predictive performances of the optimal MTP-EN model and the EN model [average area under the receiver operating curve (AUROC) = 0.93]. EN models built to the integrated dataset and the adaptive dataset yielded identically high AUROC values (average AUROC = 0.91), while the innate data EN model performed poorly (average AUROC = 0.62). Results also indicated that integration of adaptive and innate biomarkers did not outperform the adaptive biomarkers alone (Likelihood Ratio Test χ2 = 6.09, p = 0.808). From a total of 193 variables, the level of HLA-DR on ESAT6/CFP10-specific Th1 cytokine-expressing CD4 cells was the strongest biomarker for recent M.tb infection. The discriminatory ability of this variable was confirmed in both tree-based models. A single biomarker measuring M.tb-specific T cell activation yielded excellent diagnostic potential to distinguish between recent and remote M.tb infection.

Parvovirus B19 Seroprevalence in Women with Bad Obstetric History in Kirkuk.

Background: In Iraqi community, abnormal pregnancy form a major social ans psychological and health problem. The underlying etiology of this health phenomenon was varied and includes sets of infections and autoimmune diseases. Globally human parvovirus 19 infection is common and the infection attribute to bad obstetric outcomes. Global maternal parvovirus B19 remote infection rate was with a range of 13.2% to 97.9%, while the range of acute infection was 0.5% to 97.9%. In Arab countries, the IgG seroprevalence was 53.3% to 74%, while IgM seroprevalence range was 2.2% to 84%. Objective: To evaluate the role of Parvovirus B19 as an etiology of bad obstetric outcome in women in Kirkuk, Iraq. Materials and Methods: Descriptive Case Control Study. Women included in the study were recruited from Kirkuk General Hospital and their age ranged from 14 to 48 years. A 663 women were included in the study and 237 of them were none pregnant, while the pregnant were 215. Additionally, the study included 211 women with inevitable abortion. A control group (306 women) women with history of normal pregnancy (Pregnant=149; non-pregnant=157). Clinical and laboratory investigations were conducted on all patients and control groups to exclude other causes [7]. Medical and obstetric data and demographic characteristics gathered through interview according to previously designed questionnaire [7]. ELISA kits were used to determine Parvovirus B19 IgM and IgG antibodies. Results: The overall parvovirus seroprevalence was 93% and with no significant difference between women with normal (89.5%) and those with abnormal (93.1%) pregnancy outcomes . In addition, parvovirus IgM overall seroprevalence was 56.3%. Furthermore, current parvovirus infection was higher in women with BOH (52.6%) than that in women with normal pregnancy (49.7%) outcomes. Parvovirus IgM seroprevalence was 52.6% in women with BOH and 49.7% in women with normal pregnancy, however, the difference was not statistically significant. In contrast, the acute infection with parvovirus was significantly (X2=11.8, P=0.001) lower in women with normal pregnancy (49.7%) than in those with inevitable abortion (64.9%), While IgG seroprevalence difference was not significant between the two groups. Infection seroprevalence was more frequent in housewife, uneducated women, large family size, non-smoker, rural area, non animal exposure, repeated abortion, congenital anomalies, and anaemia. Conclusion: Parvovirus B19 infection may be with bad obstetric outcomes if occurred during pregnancy and OR confirm a significant association of the infection with parvovirus with smoking, occupation, crowding index, education, animal exposure and number of repeated abortion.

Multidimensional analysis of immune response identified biomarkers of recent Mycobacterium tuberculosis infection

The risk of tuberculosis (TB) disease is higher in individuals with recent Mycobacterium tuberculosis (M.tb) infection compared to individuals with more remote, established infection. We aimed to define blood-based biomarkers to distinguish between recent and remote infection, which would allow targeting of recently infected individuals for preventive TB treatment. We hypothesized that integration of multiple immune measurements would outperform the diagnostic performance of a single biomarker. Analysis was performed on different components of the immune system, including adaptive and innate responses to my-cobacteria, measured on recently and remotely M.tb infected adolescents. The datasets were standardized using variance stabilizing (vast) scaling and missing values were imputed using a multiple factor analysis-based approach. For data integration, we compared the performance of a Multiple Tuning Parameter Elastic Net (MTP-EN) to a standard EN model, which was built to the single datasets. Biomarkers with non-zero coefficients from the optimal single data EN models were then isolated to build logistic regression models. A decision tree and random forest model were used for statistical validation. We found no difference in the predictive performances of the optimal MTP-EN model and the EN model [average area under the receiver operating curve (AUROC)=0.93]. EN models built to the integrated dataset and the adaptive dataset yielded identically high AUROC values (average AUROC=0.91), while the innate data EN model performed poorly (average AUROC=0.62). Results also indicated that integration of adaptive and innate biomarkers did not outperform the adaptive biomarkers alone (Likelihood Ratio Test χ2=6.09, p=0.808). From a total of 193 variables, the level of HLA-DR on ESAT6/CFP10-specific Th1 cytokine-expressing CD4 cells was the strongest biomarker for recent M.tb infection. The discriminatory ability of this variable was confirmed in both tree-based models.A single biomarker measuring M.tb-specific T cell activation yielded excellent diagnostic potential to distinguish between recent and remote M.tb infection.

Immune profiling of Mycobacterium tuberculosis-specific T cells in recent and remote infection

BackgroundRecent Mycobacterium tuberculosis (M.tb) infection is associated with a higher risk of progression to tuberculosis disease, compared to persistent infection after remote exposure. However, current immunodiagnostic tools fail to distinguish between recent and remote infection. We aimed to characterise the immunobiology associated with acquisition of M.tb infection and identify a biomarker that can distinguish recent from remote infection.MethodsHealthy South African adolescents were serially tested with QuantiFERON-TB Gold to define recent (QuantiFERON-TB conversion <6 months) and persistent (QuantiFERON-TB+ for >1.5 year) infection. We characterized M.tb-specific CD4 T cell functional (IFN-γ, TNF, IL-2, CD107, CD154), memory (CD45RA, CCR7, CD27, KLRG-1) and activation (HLA-DR) profiles by flow cytometry after CFP-10/ESAT-6 peptide pool or M.tb lysate stimulation. We then assessed the diagnostic performance of immune profiles that were differentially expressed between individuals with recent or persistent QuantiFERON-TB+.FindingsCFP-10/ESAT-6-specific CD4 T cell activation but not functional or memory phenotypes distinguished between individuals with recent and persistent QuantiFERON-TB+. In response to M.tb lysate, recent QuantiFERON-TB+ individuals had lower proportions of highly differentiated IFN-γ+TNF+ CD4 T cells expressing a KLRG-1+ effector phenotype and higher proportions of early differentiated IFN-γ-TNF+IL-2+ and activated CD4 T cells compared to persistent QuantiFERON-TB+ individuals. Among all differentially expressed T cell features CFP-10/ESAT-6-specific CD4 T cell activation was the best performing diagnostic biomarker of recent infection.InterpretationRecent M.tb infection is associated with highly activated and moderately differentiated functional M.tb-specific T cell subsets, that can be used as biomarkers to distinguish between recent and remote infection.

How to treat arteriovenous graft infection: total versus partial graft excision

Introduction: Arteriovenous graft (AVG) infection can result in life-threatening sepsis and loss of vascular access. A retrospective study was performed to establish an appropriate treatment strategy for AVG infection. Methods: A total of 50 cases of AVG infection were treated between January 2005 and June 2016. The surgical methods used were total graft excision (TGE) (n = 34), or partial graft excision (PGE) with interposition graft (n = 16). Results: Infection was noted at a puncture site (n = 22), a prior incision for surgery or endovascular therapy (n = 20), and abandoned (currently unused) grafts (n = 5). Infection occurred within 1 month after AVG creation (n = 1), or any intervention (n = 14), and more than 1 month after creation or intervention (n = 35). Simultaneous remote infection was identified in 7 patients, 2 of whom underwent an operation for infective endocarditis and spondylitis. After PGE, 5 patients (5/16, 31.2%) having recurrent infection were treated with further graft excision; however, no patient showed life-threatening complications. After TGE, a central venous catheter (CVC) was inserted and used for a median period of 90 days. Among 34 patients who underwent TGE, new vascular access was created in 18 patients at a median period of 2 months later, and 12 patients continued to use a CVC until last follow-up or death. Conclusions: PGE could be a treatment option for AVG infection to achieve both infection eradication and vascular access preservation in selected patients. Because of a higher risk of recurrent infection, sufficient surgical removal and careful postoperative management are warranted.

Clostridium septicum: An Unusual Link to a Lower Gastrointestinal Bleed

Clostridium septicum is a highly virulent pathogen which is associated with colorectal malignancy, hematological malignancy, immunosuppression, diabetes mellitus and cyclical neutropenia. Presentation may include disseminated clostridial infection in the form of septicemia, gas gangrene, and mycotic aortic aneurysms. We report the case of a 62-year-old female presenting with necrotizing fasciitis of her left thigh and subsequently developing rectal bleeding. While she was being treated with empiric antibiotics, her blood culture was found to be positive for C. septicum. We would like to highlight the importance of early colorectal cancer screening in minimizing the occurrence of undetected tumors which provide an optimal growth environment for C. septicum, leading to localized and/or remote infection.