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Blastomyces dermatitidis is a thermally dimorphic fungus that is capable of causing pulmonary and extra-pulmonary disease, including infections of the central nervous system (CNS). Diagnosis of CNS blastomycosis with non-invasive testing can be difficult, and a surgical biopsy may ultimately be required for microbiological and/or histopathological confirmation. A case of B. dermatitidis meningitis is presented where the diagnosis was made by testing cerebrospinal fluid (CSF) using the MVista® Blastomyces Quantitative Antigen Enzyme Immunoassay test. The utility of performing this test on CSF for diagnosis of CNS mass lesions/abscesses caused by B. dermatitidis in the absence of associated meningitis remains unclear. Cross reaction of the Blastomyces antigen test with other dimorphic fungi is a concern, necessitating that positive test results are interpreted in the context of the patient's exposure and travel history.

Background. Immune parameters (IP) have been extensively studied to distinguish between latent tuberculosis (LTBI) and active tuberculosis (TB). Objective. To determine the IP associated with LTBI, compared to active TB and individuals not infected by M. tuberculosis published in literature. Methods. We conducted a systematic search using Google Scholar and PubMed databases, combining the MeSH terms latent tuberculosis, Mycobacterium tuberculosis, cytokines, and biological markers, with the free terms, biomarkers and cytokines. Spanish, English, and Portuguese articles comparing the concentration of IP associated with LTBI, either in plasma/serum or in vitro, in adults and nonimmunocompromised versus individuals with TB or without M. tuberculosis infection between 2006 July and 2018 July were included. Two blinded reviewers carried out the searches, read the abstracts, and selected the articles for analysis. Participants’ information, diagnostic criteria, IP, detection methods, and biases were collected. Results. We analyzed 36 articles (of 637 abstracts) with 93 different biomarkers in different samples. We found 24 parameters that were increased only in active TB (TGF-α, CSF3, CSF2, CCL1 [I-309], IL-7, TGF-β1, CCL3 [MIP-1α], sIL-2R, TNF-β, CCL7 [MCP-3], IFN-α, fractalkine, I-TAG, CCL8 [MCP-2], CCL21 [6Ckine], PDGF, IL-22, VEGF-A, LXA4, PGE2, PGF2α, sCD163, sCD14, and 15-Epi-LXA4), five were elevated in LTBI (IL-5, IL-17F, IL-1, CCL20 [MIP-3α], and ICAM-1), and two substances were increased among uninfected individuals (IL-23 and basic FGF). We found high heterogeneity between studies including failure to account for the time/illness of the individuals studied; varied samples and protocols; different clinical classification of TB; different laboratory methods for IP detection, which in turn leads to variable units of measurement and assay sensitivities; and selection bias regarding TST and booster effect. None of the studies adjusted the analysis for the effect of ethnicity. Conclusions. It is mandatory to harmonize the study of immune parameters for LTBI diagnosis. This systematic review is registered with PROSPERO CRD42017073289.

Colombia has an underreporting of 30% of the total cases, according to World Health Organization (WHO) estimations. In 2016, successful tuberculosis (TB) treatment rate was 70%, and the mortality rate ranged between 3.5% and 10%. In 2015, Colombia adopted and adapted the End TB strategy and set a target of 50% reduction in incidence and mortality by 2035 compared with 2015. The aims of this study were: To evaluate whether Colombia will be able to achieve the goals of TB incidence and mortality by 2050, using the current strategies; and whether the implementation of new screening, diagnosis and TB treatment strategies will allow to achieve those WHO targets. An ecological study was conducted using TB case-notification, successful treatment and mortality rates from the last 8 years (2009–17). System dynamics analysis was performed using simulated scenarios: (1) continuation with the same trends following the trajectory of the last 8 years (Status quo) and (2) modification of the targets between 2017 through 2050, assuming the implementation of multimodal strategies to increase the screening, to improve the early diagnosis and to improve the treatment adherence. Following the current strategies, it is projected that Colombia will not achieve the End TB strategy targets. Achieving the goal of TB incidence of 10/100 000 by 2050 will only be possible by implementing combined strategies for increasing screening of people with respiratory symptoms, improving access to rapid diagnostic tests and improving treatment adherence. Therefore, it is necessary to design and implement simultaneous strategies according to the population needs and resources, in order to stride towards the End TB targets.

March 24 was World Tuberculosis Day and Canada still has much to do to fulfil recent commitments[1][1] to eliminate tuberculosis (TB), a disease that has long required collaboration and coherence to address effectively its multiple determinants. [2][2],[3][3] As suggested by Essue and colleagues in

Background In the development of administrative data case-definitions for HIV, it is important to understand the contribution of each data source to prevalence estimates, especially as it pertains to generalizability of methods. Methods HIV case-definitions were constructed from four population-based databases available in Manitoba: physician claims, hospital discharge, pharmaceutical dispensations, and provincial laboratory tests. Performance was assessed using sensitivity, specificity, positive/negative predictive value (PPV & NPV), and Youden’s index (YI). Cases identified by HIV case-definitions, and those reported to public health surveillance were compared using annualized incidence. The distribution of those flagged as HIV-positive was compared by database. Results The best performing case-definition (YI 0.71) was two or more HIV diagnoses in two years in physician claims, or in hospital discharge abstracts; or 14 or more HAART dispensations in two years; or one positive HIV laboratory. Sensitivity, specificity, PPV and NPV was 82.3% (95%CI: 79.1%-85.5%), 86.8% (95%CI: 84.9%-88.7%), 74.1% (95%CI: 70.6%-77.6%), 91.4% (95%CI: 89.8%-93.1%), respectively. Annualized incidence (2009–2015) calculated from this case-definition was 7.4/100,000 persons (95%CI: 6.8–8.1)]; annualized incidence calculated from surveillance data was 7.7/100,000 persons (95%CI: 7.1–8.3). Approximately 76% of cases would have been flagged through a positive laboratory; 43% through pharmaceutical claims; 34% through physician claims; and 11% through hospital abstracts. 95% of cases would have been flagged through the combination of laboratory and pharmaceutical databases. Only 4% of cases were flagged in all four data sources. Conclusion Although the combination of four databases produced the most complete prevalence snapshot, laboratory data was the most important contributor. The combination of laboratory and pharmaceutical databases would have identified the predominant majority of cases in our sample. Findings can be used to inform the construction of administrative data cohorts where the availability of population-based data sources may be more limited. Disclosure No significant relationships.

Background The incidence of Staphylococcus aureus infective endocarditis (IE) is steadily rising due to advances in health care delivery. Routine echocardiography is essential in the management of Staphylococcus aureus bacteremia (SAB). The aim of this retrospective cohort study was to characterize the real-world use of echocardiography in adult patients with SAB and native valve S aureus IE. Methods Using an academic hospital microbiological database, all cases of SAB in adults between 2010 and 2016 were identified. Demographic, echocardiographic, and clinical features were recorded. Results A total of 738 episodes of SAB were identified, of which 504 (68%) patients underwent transthoracic echocardiography (TTE) within 30 days. Of 73 patients with definite IE, 46 (63%) patients had definite IE diagnosed on the initial TTE. An additional 14 (19%) patients had definite IE diagnosed on repeat TTE, 6 (8%) on transesophageal echocardiography (TEE), and 7 (10%) were diagnosed without fulfilling Duke echocardiographic criteria. The yield of repeat TTE was comparable to that of TEE for identifying new vegetations not identified on the initial TTE (17% vs 21%, P = .78). Conclusions Most cases of IE in SAB were identified using TTE alone, with repeat TTE improving the diagnostic yield in the setting of clinical decompensation.

The current scale of public and private testing cannot be expected to meet the emerging need for higher levels of community-level and repeated screening of asymptomatic Canadians for SARS-CoV-2. Rapid point-of-care techniques are increasingly being offered to fill the gap in screening levels required to identify undiagnosed individuals with high viral loads. However, rapid, point-of-care tests often have lower sensitivity in practice. Reverse transcription loop-mediated isothermal amplification (RT-LAMP) for SARS-CoV-2 has proven sensitive and specific and provides visual results in minutes. Using a commercially available kit for RT-LAMP and primer set targetting nucleocapsid (N), we tested a blinded set of 101 archived nasopharyngeal (NP) swab samples with known RT-PCR results. RT-LAMP reactions were incubated at 65 °C for 30 min, using heat-inactivated nasopharyngeal swab sample in viral transport medium, diluted tenfold in water, as input. RT-LAMP agreed with all RT-PCR defined negatives (N = 51), and all positives with cycle threshold (Ct) less than 20 (N = 24), 65% of positives with Ct between 20-30 (N = 17), and no positives with Ct greater than 30 (N = 9). RT-LAMP requires fewer and different core components, so may not compete directly with the mainline testing workflow, preserving precious central laboratory resources for those with the greatest need. Careful messaging must be provided when using less-sensitive tests, so that people are not falsely reassured by negative results, but this caveat must be weighed against the clear benefits of reliably identifying those with high levels of virus in prioritized samples at the point of care.

This study aims to analyze survival, repeat hospitalization, and risk factors for surgically treated left-sided endocarditis. Retrospective review of all 166 (114 native and 52 prosthetic) patients operated between January 2004 and March 2015 was performed. Long-term survival and repeat hospitalization data for 134 of 166 patients were obtained via linked clinical databases with the Manitoba Centre for Health Policy. Kaplan-Meier estimates of survival and hospital readmission and Cox multivariable regression analysis of factors influencing outcomes were performed. Survival at 1 and 5 years was 91% and 80%, respectively, and major adverse prosthesis-related event repeat hospitalization rates were 12% and 21%, respectively. Repeat hospitalization because of endocarditis was 7% and 11% at 1 and 5 years, respectively. Survival and repeat hospitalization were similar for aortic and mitral valves. Survival after surgically treated endocarditis was similar to survival for age-, sex-, and valve-matched surgical valve replacements for noninfectious indications (P = 0.53). Viridans Streptococci was the most common organism in native valve endocarditis, and culture negative endocarditis was most common in prosthetic valves. Prosthetic valve endocarditis (P 0.01) and preoperative renal dysfunction (P 0.01) were risk factors for in-hospital mortality and major postoperative adverse events. Diabetes and renal dysfunction were associated with poor long-term survival, functional survival, and repeat hospitalization. This analysis suggests that surgery remains a very effective tool in management of these complex patients in terms of survival and major adverse prosthesis-related event repeat hospitalization.

Infective endocarditis (IE) is a life-threatening disease. Considered the gold standard for the diagnosis of IE, the modified Duke criteria rely on echocardiographic findings to satisfy its major criterion. Echocardiography is an invaluable tool in the evaluation of patients with suspected IE but suffers from certain limitations. For example, it cannot differentiate vegetation from clot, or between infected and noninfected vegetation, and may miss vegetation and periannular extensions in the presence of prosthetic material. Therefore, alternative cardiac imaging modalities are needed. Nuclear imaging, particularly 18 F-fluorodesoxyglucose positron emission tomography–computed tomography (CT), is becoming increasingly popular in the evaluation of patients for IE and has shown promise in diagnosing valvular and device-related IE when echocardiography results were inconclusive. Other techniques such as radiolabeled leukocyte scintigraphy and single-photon emission computed tomography with or without CT are less well studied, however. Cardiac CT angiography is also evolving as a powerful supplementary tool to echocardiography for the detection of perivalvular complications of IE and for preoperative evaluation of coronary anatomy. The combination of cardiac CT angiography and echocardiography is superior to either test alone in the diagnosis of IE and its complications. Although brain magnetic resonance imaging may impact prognosis and clinical management by identifying cerebral emboli in patients with IE, the role of cardiac and abdominal magnetic resonance imaging is less clear. In conclusion, with these additional diagnostic tools at our disposal, the diagnosis of IE may be achieved in a more timely and accurate manner to secure better clinical outcomes.

Understanding patterns of serological testing for hepatitis B & C, and syphilis among HIV-positive individuals, prior to HIV diagnosis, can inform HIV diagnosis, engagement and prevention strategies. This was a population-based, retrospective analysis of prior serological testing among HIV-positive individuals in Manitoba, Canada. HIV cases were age-, sex- and region-matched to HIV-negative controls at a 1:5 ratio. Conditional logistic regression was used to examine previous serological tests and HIV status. Odds ratios (ORs) and their 95% confidence intervals (95% CI) were reported. A total of 193 cases and 965 controls were included. In the 5 years prior to diagnosis, 50% of cases had at least one test, compared to 26% of controls. Compared to those who did not have serological testing in the 5 years prior to HIV infection, those who had one serological test were at twice the odds of being HIV positive (OR: 1.9, 95% CI: 1.2-2.9), while those with 2 or more tests were at even higher odds (OR: 5.5, 95%CI: 3.7-8.4). HIV cases had higher serological testing rates. Interactions between public health and other healthcare providers should be strengthened.

Introduction Determining vaccine responsiveness is challenging in immune compromised individuals. The microbead array (MBA) assay is a rapid, inexpensive test for evaluating influenza vaccine immunogenicity. MBA performance was compared to hemagglutination inhibition assay (HAI) utilizing HIV seropositive vaccine recipient specimens. Methods CTN 253 evaluated standard dose, single antigen, inactivated split adjuvanted (AS03(A)) H1N1 influenza vaccine (Arepanrix) vs standard dose plus booster. CTN237 evaluated three doses of a seasonal, trivalent killed split non-adjuvanted influenza vaccine (Fluviral). Samples of convenience from 75 CTN 253 and 58 CTN 237 participants were evaluated by MBA and HAI. MBA seroreactivity cut-offs of 500 and 1000 mean fluorescent intensity were used to compare those derived by HAI [titer ≥40 (seroprotection) and 4-fold titer increase from baseline (seroconversion)]. Results CTN253: Using a MBA cut-off of 500, 75% and 59% had seroreactive titers at visit 2 and 78% and 61% at visit 3 for the single versus double dose study arms. Many participants were categorized differently by the HAI and MBA tests, with raw agreement of 59% at visit 2 and 57% at visit 3. CTN 237: Baseline MBA medians (IQR) were 803 (12-2626) for the A/Brisbane strain and 460 (14-1758) for the B/Florida strain. Using a cut-off of 500 yielded for the A/Brisbane strain seroreactivity rates of 44%, 58%, and 63% were observed for the three doses of vaccine tested. The raw agreement was 47%. B/Florida strain analyses yielded similar results. For all strains assessed in both studies, no relationship between MBA values and baseline variables was identified. Conclusion The concordance of results between the MBA assay and the HAI assay is very low. MBA assay may be more sensitive than the HAI assay suggesting that it was either detecting more false-positive results and/or that the HAI assay had more false negative.

HIV and pneumonia infections have both been shown to negatively impact lung function. However, evidence of the role of inflammation on lung dysfunction in HIV and pneumonia co-infected individuals remains limited. We aimed to systematically review the association of inflammatory markers and lung abnormalities in HIV and pneumonia co-infected individuals. This systematic review was registered with the International Prospective Register of Systematic Reviews on August 15, 2017 (registration number CRD42017069254) and used 4 databases (Cochrane Central Register of Controlled Trials, PubMed Central, Clinical Trials.gov and Google Scholar). All clinical trial, observational, and comparative studies targeting adult (> 18 years old) populations with HIV, pneumonia, or both, that report on immune response (cytokine, chemokine, or biomarker), and lung abnormality as an outcome were eligible. Data selection, risk of bias and extraction were performed independently by 2 blinded reviewers. Due to heterogeneity among the articles, a qualitative synthesis was performed. Our search strategy identified 4454 articles of which, 7 met our inclusion criteria. All of the studies investigated the ability of circulating biomarkers to predict lung damage in HIV. None of the articles included patients with both HIV and pneumonia, nor pneumonia alone. Markers of inflammation (IL-6, TNF-α, CRP), innate defense (cathelicidin), monocyte and macrophage activation (sCD14, sCD163 and, IL-2sRα), endothelial dysfunction (ET-1) and general immune health (CD4/CD8 ratio) were associated with lung abnormalities in HIV. This review highlights the lack of available information regarding the impact of inflammatory mediators on lung function in HIV and pneumonia populations, therefore opportunities to prevent lung damage with available anti-inflammatory treatment or to investigate new ones still remain.

Although Canada has one of the lowest tuberculosis incidence rates in the world, certain groups are disproportionately affected, including foreign born people from high incidence countries. The Winnipeg Regional Health Authority has initiated a process to decentralize latent tuberculosis infection (LTBI) management at primary care clinics in Winnipeg. One of these clinics is BridgeCare Clinic which provides services to government-assisted refugees. The present study describes the BridgeCare Clinic LTBI program and reviews program outcomes from January 2015 to October 2016. Refugees at BridgeCare Clinic receive comprehensive care, including LTBI screening and treatment. The LTBI program is managed by physicians, nurse practitioners, and primary care nurses under a patient-centered model of care. An accessible interpretation service, education to clients, and laboratory sampling at the clinic with free IGRA testing are important components of the program. Anonymized data on client outcomes were statistically analyzed and qualitative interviews were conducted with senior staff. During the study period, 274 IGRA tests were ordered with 158 negative results (57.7%) and 101 positive results (36.9%). Of 45 clients eligible (from January to December 2015) for LTBI treatment, 11 (24.4%) declined to receive treatment and 34 (75.6%) started treatment. Twenty-seven (79.4%) clients completed treatment, 3 (8.8%) clients moved out of province, and 4 (11.8%) did not complete treatment. The most recent World Health Organization strategy for tuberculosis control calls for integrated, patient-centered care and prevention. Aligned with these WHO recommendations, our experience suggests that LTBI care and treatment can be delivered effectively in a primary care setting using an integrated patient-centered approach.

Background Knowledge translation (KT) and related terms have variously been defined as process and as products. In this paper we contribute to debates on effective KT, specifically knowledge brokering, by describing an adaptation of Program Science that aligns with the real-world of public health activities. Main abstract We describe an adaptation of the Program Science framework to our knowledge translation and brokering planning and projects at the National Collaborating Centre for Infectious Diseases. The systematic approach allows for layering of knowledge year to year and translating knowledge from one infectious disease content area to another. Using a recent forum on syphilis outbreaks as an example, we also demonstrate the value of using Program Science to shape the design and delivery of the knowledge brokering event. Conclusion The use of scientific knowledge to improve public health program design, implementation and evaluation forms the basis for the program science framework. Providing the right public health information to the right audience at the right time can foster long-term outcomes of networks and new partnerships which can potentially improve delivery of public health services.

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The high prevalence of substance use among HIV-infected individuals creates numerous challenges to patient care. This study was undertaken in order to understand the impact of substance use on care outcomes for HIV-infected individuals in Manitoba. Clinical records of 564 HIV-infected individuals in care at Health Sciences Centre in Winnipeg, Manitoba were reviewed. Clinical data were extracted from patient charts for substance users (illicit substance users, alcohol abusers and chronic users of opioids or benzodiazepines) and non-users. Substance users and non-users were analysed using chi-square analysis and logistic regression models to compare basic socio-demographic and clinic variables. Chi-square and analysis of variance were used to compare a subset of substance users based on similar socio-demographic and clinical characteristics. Among HIV-infected individuals in Manitoba, 38% were substance users with over-representation by Aboriginals, females, young adults and residents of Winnipeg's core areas. Opioids and benzodiazepines were the most commonly used substances with the majority of substance users having used multiple classes of substances in their lifetime. Substance users were more likely than non-users to have missed clinic appointments. Among substance users, missed appointments were more common among those who self-identified as Aboriginal, female, young adults, residents of Winnipeg's core areas, heterosexuals and those who had abused alcohol or cocaine/crack. Aboriginal substance users were also less likely to achieve viral load suppression compared to non-Aboriginal substance users. With the high prevalence of substance use among HIV-infected individuals in Manitoba, it is important to identify at-risk individuals in order to implement appropriate care strategies and improve treatment adherence and health outcomes.

Tetanus is a life-threatening clinical syndrome that commonly presents with muscular spasms, rigidity, and autonomic instability. It is considered rare in industrialized countries, and tetanus occurring secondary to dental abscesses, procedures, or infections has been infrequently reported. We describe the case of a patient inadequately immunized for tetanus, who presented to the emergency department with muscular spasms, rigidity, and autonomic instability in the setting of an odontogenic infection. A clinical diagnosis of tetanus was made and subsequently managed successfully.

Transmitted by the bite of female sandflies, leishmaniasis is a protozoal infection. Visceral leishmaniasis, which is usually transmitted by Leishmania donovani and Leishmania infantum, occurs when the reticuloendothelial system is affected, and is more severe in HIV-infected patients because it increases HIV viral replication, as described in this case report. The authors also describe gastrointestinal complications that occurred in both this case and in other visceral leishmaniasis cases from the literature., The present report documents a 49-year-old HIV-infected man receiving antiretroviral therapy with a suboptimal immune response and a CD4 count of 95 cells/mm3, despite virological suppression. Investigation of bone marrow was conducted and yielded a diagnosis of visceral leishmaniasis. The clinical course was complicated by gastrointestinal involvment and relapse occurred after amphotericin B therapy. With the addition of miltefosine, the patient no longer presented with bone marrow amastigotes, and displayed an increased CD4 count and negative Leishmania polymerase chain reaction results. The present case highlights atypical presentation of visceral leishmaniasis, including poor immune reconstitution and gastrointestinal involvement. The high likelihood of relapse and response to combination therapy are illustrated.

During HIV infection, large amounts of progeny viral particles, including infectious virus and a large proportion of defective viral particles, are produced. Despite of the critical role of the infectious viruses in infection and pathogenesis in vivo, whether and how those defective viral particles, especially the virus-associated envelope glycoprotein (vEnv), would impact viral infection remains elusive. In this study, we investigated the effect of vEnv on HIV-infected T cells and demonstrated that the vEnv was able to stimulate HIV transcription in HIV-infected cells, including peripheral blood mononuclear cells (PBMCs) isolated from HIV patients. This vEnv-mediated HIV transcription activation is mediated primarily through the interaction between vEnv and CD4/coreceptors (CCR5 or CXCR4). Through transcriptome analysis, we found that numerous cellular gene products involved in various signaling pathways were modulated by vEnv. Among them, we have further identified a cellular microRNA miR181A2, which is downregulated upon vEnv treatment, resulting in increased HIV LTR histone H3 acetylation and HIV transcription. Furthermore, we also found a vEnv-modulated cellular histone deacetylase, HDAC10, whose downregulation is associated with the increased infectivity of progeny viruses. Altogether, these findings provide evidence of the important role vEnv plays in modulating cellular environments and facilitating HIV expression and infection.

SUMMARYThe main aim was to measure the incidence of latent tuberculosis infection (LTBI) and identify risk factors associated with infection. In addition, we determined the number needed to screen (NNS) to identify LTBI and active tuberculosis. We followed 129 prisoners for 2 years following a negative two-step tuberculin skin test (TST). The cumulative incidence of TST conversion over 2 years was 29·5% (38/129), among the new TST converters, nine developed active TB. Among persons with no evidence of LTBI, the NNS to identify a LTBI case was 3·4 and an active TB case was 14·3. The adjusted risk factors for LTBI conversion were incarceration in prison number 1, being formerly incarcerated, and overweight. In conclusion, prisoners have higher risk of LTBI acquisition compared with high-risk groups, such as HIV-infected individuals and children for whom LTBI testing should be performed according to World Health Organization guidance. The high conversion rate is associated with high incidence of active TB disease, and therefore we recommend mandatory LTBI screening at the time of prison entry. Individuals with a negative TST at the time of entry to prison are at high risk of acquiring infection, and should therefore be followed in order to detect convertors and offer LTBI treatment. This approach has a very low NNS for each identified case, and it can be utilized to decrease development of active TB disease and transmission.

We describe a dramatic presentation of meningoencephalitis, in a young Aboriginal male from Northern Manitoba, due to infection with the Snowshoe hare virus, a member of the California serogroup viruses. Snowshoe hare virus represents a rare cause of meningoencephalitis, and, to date, few Canadian cases have been described in the literature.

These strains are more likely to cause invasive infection, which is an emerging public health concern as incidence and disease severity are on the rise., The incidence of group C and G Streptococcus (GCGS) bacteremia, which is associated with severe disease and death, is increasing. We characterized clinical features, outcomes, and genetic determinants of GCGS bacteremia for 89 patients in Winnipeg, Manitoba, Canada, who had GCGS bacteremia during 2012–2014. Of the 89 patients, 51% had bacteremia from skin and soft tissue, 70% had severe disease features, and 20% died. Whole-genome sequencing analysis was performed on isolates derived from 89 blood samples and 33 respiratory sample controls: 5 closely related genetic lineages were identified as being more likely to cause invasive disease than non-clade isolates (83% vs. 57%, p = 0.002). Virulence factors cbp, fbp, speG, sicG, gfbA, and bca clustered clonally into these clades. A clonal distribution of virulence factors may account for severe and fatal cases of bacteremia caused by invasive GCGS.

Echocardiography is an important diagnostic tool in evaluating a patient with Staphylococcus aureus bacteremia (SAB) for diagnosing infective endocarditis (IE). We sought to compare the utility of transthoracic echocardiography (TTE) with transesophageal echocardiography (TEE) in screening for IE in patients with SAB. We performed a retrospective chart review of 285 adult patients from two tertiary care hospitals with at least one positive blood culture for S. aureus between 2010 and 2012. Patients who underwent echocardiography were divided into two groups: TTE (screened with TTE only) and TEE (screened with both TTE and TEE). The demographic factors and clinical outcomes were compared between the groups. Of the 285 charts reviewed, 213 (74.7 %) patients were screened with echocardiography: 183 (85.9 %) were screened with TTE alone and 30 (14.1 %) were screened with both TTE and TEE. TEE disclosed more cases of definite IE than TTE (8 [26.7 %] vs. 22 [12.0 %], p = 0.046). The TEE group had higher mortality than the TTE group (15 [50.0 %] vs. 43 [23.5 %], p = 0.004). In patients with definite IE, mortality was higher in the TEE group than in the TTE group (6 [75.0 %] vs. 6 [27.3 %], p = 0.034). TEE discovered additional findings that were missed by TTE in 36.7 % of cases and refuted the findings of TTE in 13.3 % of cases. We do not support the routine use of TEE in patients with uncomplicated SAB. High-risk patients in which IE is a serious consideration should undergo investigation with TEE.

Background HIV patients face higher rates of morbidity compared with the general population, largely due to the earlier development of age related diseases (cardiovascular, kidney, and liver disease). While it is likely that chronic immune activation and inflammation are the main contributors to this process, it’s relation to lung injury in HIV remains unknown. Despite restoration of systemic immune function following Antiretroviral Therapy, the risk for lower respiratory tract infection remain elevated in the HIV population. The objective of the study was to assess the relationship between pulmonary inflammation and lung injury. Methods A prospective cohort study was performed, participants include patients hospitalized in Hospital Universitario San Vicente Fundación and Clínica SOMA, in Colombia. Patients were eligible if they were over the age of 18 and had a documented HIV infection or if they have HIV with newly diagnosed community acquired pneumonia (CAP). The main exclusion criteria were chronic lung disease and immunosuppression that is not due to HIV. Patients belonged to two groups: HIV and HIV + CAP. Plasma, sputum samples and pulmonary function test measurements (PFT) were retrieved within 48 hours of hospital admission and at one month follow-up. The concentrations of 13 biomarkers were measured and correlated with PFT values, followed by a comparison between the two groups. Results Principle Component Analysis revealed that CCL3, CCL4, BAFF, APRIL, and TIMP-1 accounts for the majority of the variation between the two groups. Furthermore, Kruskal–Wallis testing demonstrates that BAFF and CCL3 are elevated in the HIV + CAP group, compared with the HIV group (P < 0.005). Other markers of bacterial translocation and monocyte activation did not differ between these groups. FVC and FEV1 measurements are lower in the HIV + CAP group compared with the HIV group, while FEV1/FVC remain constant. Conclusion The results of this study identify a unique constellation of biomarkers in HIV patients with CAP, this constellation of biomarkers consists of pro-inflammatory cytokines and regulators of extracellular matrix remodeling, hinting at the occurrence of an inflammatory and tissue injuring process in the lungs. This is supported by the restrictive ventilation pattern seen in this group of patients. Disclosures All authors: No reported disclosures.

The fluoroquinolones (FQs) are important agents for the treatment of mycobacterial infections. In leprosy, the use of FQs has enabled a dramatic shortening of formerly long and complicated therapy. Both animal and human studies support the inclusion of certain FQs as a cornerstone of leprosy therapy. In tuberculosis (TB), particularly in multidrug-resistant (MDR) infections, the place of the major antimycobacterial FQs is less clear as there is widespread resistance to these agents in areas of the world in which MDR-TB and extensively drug-resistant (XDR)-TB are prevalent, particularly in Southeast Asia. The place of the newly developed FQ-related diarylquinoline compound known as bedaquiline in the treatment of drug-resistant TB is unclear; however, human studies suggest that it might be effective for this indication.

Human immunodeficiency virus (HIV)-infected individuals are more susceptible to respiratory tract infections by other infectious agents (viruses, bacteria, parasites, and fungi) as their disease progresses to acquired immunodeficiency syndrome. Despite effective antiretroviral therapy, bacterial pneumonia (the most frequently occurring HIV-associated pulmonary illness) remains a common cause of morbidity and mortality in the HIV-infected population. Over the last few decades, studies have looked at the role of atypical bacterial pneumonia (i.e. pneumonia that causes an atypical clinical presentation or responds differently to typical therapeutics) in association with HIV infection. Due to the lack of available diagnostic strategies, the lack of consideration, and the declining immunity of the patient, HIV co-infections with atypical bacteria are currently believed to be underreported. Thus, following an extensive database search, this review aimed to highlight the current knowledge and gaps regarding atypical bacterial pneumonia in HIV. The authors discuss the prevalence of Chlamydophila pneumoniae, Mycoplasma pneumoniae, Coxiella burnetii, Legionella species and others in the HIV-infected population as well as their clinical presentation, methods of detection, and treatment. Further studies looking at the role of these microbes in association with HIV are required. Increased knowledge of these atypical bacteria will lead to a more rapid diagnosis of these infections, resulting in an improved quality of life for the HIV-infected population. COL0005744

Point-of-care (POC) HIV testing has been shown to be an acceptable method for increasing HIV testing uptake. To date, no studies have examined the use of POC testing for routine HIV screening on the medicine inpatient unit. A prospective cross-sectional study was conducted over a three-month period in July, August, and October 2016 to evaluate the prevalence of undiagnosed HIV and the attitudes towards routine POC HIV testing. Patients admitted directly to medicine inpatient teaching units at a tertiary hospital in Winnipeg, Canada, were approached for participation. The POC HIV test was administered at the bedside. Reactive and indeterminate tests were confirmed with standard serological HIV testing. Participants were given a questionnaire regarding their attitudes towards POC testing on the unit. Although no cases of previously undiagnosed HIV were identified during the study period, only 35% of participants were found to have ever had HIV testing previously. The majority of participants were satisfied with the POC testing experience and would choose to have the POC testing again. Overall, the low rate of outpatient testing highlights the need for routine HIV testing on an inpatient basis.

Following the influenza epidemics, it has become clear that severity of illness is not uniform. Comorbidities and immunocompromise account for only a fraction of severe cases and do not explain the differential severity among the otherwise healthy during pandemics. During the 2009 H1N1 pandemic, a focus has been placed on better understanding of the determinants and pathogenesis of severe influenza infections. Much of the current literature has focused on viral genetics and its impact on host immunity as well as novel risk factors for severe infection (particularly within the H1N1 pandemic). The improved understanding of the cellular mechanisms and pathways involved in the pathogenesis of severe disease along with technological advances have allowed a more systematic approach to the exploration of the host genetic determinants of susceptibility and severe respiratory illness. By better defining the role of genetic variability in the immune responses to influenza, and identifying key polymorphisms that either protect against severe manifestation or those that impair the host immune response, it is possible to envision better methods to identify at-risk populations and new targets for therapeutic interventions and vaccines. This review will summarize the accumulated literature examining the immunogenetic factors associated with propensity for the development of severe pandemic H1N1 (pH1N1) manifestations. We will focus on novel and key insights gained through study of ethnic populations that appeared more vulnerable to severe disease during the 2009 H1N1 pandemic.

Introduction: Actinomyces is a relatively uncommon cause of infection of the head and neck. However, its presentation is usually atypical and can be difficult to recognize. In this case report, we present the diagnostic and therapeutic challenges that can arise from cervicofacial actinomycosis. Case presentation: A 26-year-old woman from Northern Manitoba in her second trimester of pregnancy presented to the emergency department with a 2-month history of progressive pain and swelling of her right mandible. Imaging revealed lytic lesions involving the angle and ramus of the right mandible with possibility of osteosarcoma, and she was taken for hemimandibulectomy. Intraoperative specimens revealed Actinomyces odontolyticus. She was subsequently started on piperacillin–tazobactam that was later stepped down to amoxicillin–clavulanate with radiographic and clinical improvement of her osteomyelitis. Conclusion: Cervicofacial actinomycosis may mimic several neoplastic, granulomatous and infectious conditions, and often require tissue culture for diagnosis. Therapy often necessitates a combination of surgical resection and prolonged medical therapy, which is tailored to the burden of disease in the individual patient.

Objectives This study aimed to evaluate the immuno-prophylactic and -therapeutic effect of p110δ-specific pharmacological inhibitors (CAL-101 and IC87114), either alone or in combination with amphotericin B, against experimental cutaneous leishmaniasis (CL) and visceral leishmaniasis (VL). Methods Female BALB/c mice were infected intravenously with Leishmania donovani or subcutaneously with Leishmania major Prophylactic treatment was initiated 24 h prior to infection, whereas therapeutic treatments with or without amphotericin B were initiated either 1 week or 2 weeks post-infection. At different times post-infection, mice were sacrificed and parasite burden, regulatory T cell (Treg) numbers and cytokine production were assessed in the liver, spleen, draining lymph nodes and footpads. In addition, direct cytolytic effects of the inhibitors on parasite growth in axenic cultures and inside infected and uninfected macrophages were also assessed. Results Prophylactic and therapeutic administration of p110δ pharmacological inhibitors significantly reduced cutaneous lesion (in CL) and parasite burdens (in VL and CL) in the spleens, livers and footpads of infected mice. The reduction in parasite burden was associated with a concomitant reduction in Treg numbers and cytokine production by liver, spleen and lymph node cells. Combined low-dose CAL-101 and amphotericin B therapy caused complete clearance of parasites in mice infected with L. donovani CONCLUSIONS: Our studies clearly show a novel therapeutic option for leishmaniasis based on CAL-101 monotherapy or CAL-101 and amphotericin B combination therapy. These observations have important and direct implications for antimicrobial immunotherapy and drug/vaccine development against leishmaniasis.

Background Host factors and complications have been associated with higher mortality in infective endocarditis ( IE ). We sought to develop and validate a model of clinical characteristics to predict 6‐month mortality in IE . Methods and Results Using a large multinational prospective registry of definite IE (International Collaboration on Endocarditis [ ICE ]–Prospective Cohort Study [ PCS ], 2000–2006, n=4049), a model to predict 6‐month survival was developed by Cox proportional hazards modeling with inverse probability weighting for surgery treatment and was internally validated by the bootstrapping method. This model was externally validated in an independent prospective registry ( ICE ‐ PLUS , 2008–2012, n=1197). The 6‐month mortality was 971 of 4049 (24.0%) in the ICE ‐ PCS cohort and 342 of 1197 (28.6%) in the ICE ‐ PLUS cohort. Surgery during the index hospitalization was performed in 48.1% and 54.0% of the cohorts, respectively. In the derivation model, variables related to host factors (age, dialysis), IE characteristics (prosthetic or nosocomial IE , causative organism, left‐sided valve vegetation), and IE complications (severe heart failure, stroke, paravalvular complication, and persistent bacteremia) were independently associated with 6‐month mortality, and surgery was associated with a lower risk of mortality (Harrell's C statistic 0.715). In the validation model, these variables had similar hazard ratios (Harrell's C statistic 0.682), with a similar, independent benefit of surgery (hazard ratio 0.74, 95% CI 0.62–0.89). A simplified risk model was developed by weight adjustment of these variables. Conclusions Six‐month mortality after IE is ≈25% and is predicted by host factors, IE characteristics, and IE complications. Surgery during the index hospitalization is associated with lower mortality but is performed less frequently in the highest risk patients. A simplified risk model may be used to identify specific risk subgroups in IE .

Summary: Immune Reconstitution Syndrome (IRIS) has been associated with a variety of infections in patients with human immunodeficiency virus (HIV). However, we are reporting the first case of IRIS secondary to Rhodococcus equi (R. equi) in a patient with HIV.We report the case of a 48-year-old male found to have HIV infection in the setting of Burkitt's lymphoma. While on anti-retroviral therapy and chemotherapy, he had developed IRIS secondary to R. equi that manifested as a cavitating pneumonia. This report outlines the successful management of the R. equi infection with the use of a combination of antibiotics, radiographic follow up and suppressive antibiotic while on chemotherapy. Keywords: Human immunodeficiency virus, Rhodococcus equi, Burkitt's lymphoma, Cavitating pneumonia

BACKGROUND: HIV controllers demonstrate a natural ability to control HIV replication in the absence of antiretroviral therapy. We performed a comprehensive evaluation of inflammation and T-cell activation in a demographically unique cohort of HIV controllers and noncontrollers. METHODS: Plasma concentrations of 22 cytokines and chemokines were evaluated using a multiplex bead array approach. Multicolor flow cytometry was used to measure baseline levels of T-cell activation and regulatory T cells (Tregs) and HIV-specific T-cell cytokine (interferon γ, interleukin 2) and proliferation responses. RESULTS: HIV controllers were characterized by elevated macrophage inflammatory protein 1α and low levels of interferon γ-induced protein 10, monocyte chemotactic protein 1, and Transforming growth factor beta. Activated (CD38(+) HLA DR(+)) CD4(+) and CD8(+) T cells were reduced in HIV controllers relative to noncontrollers. HIV controllers and noncontrollers had comparable proportions of Tregs within the CD4(+) T-cell compartment, but absolute Treg counts were depleted in noncontrollers. Absolute Treg counts correlated inversely with T-cell activation. Proliferative CD4(+) and CD8(+) T-cell responses directed against HIV gag epitopes were found most frequently among HIV controllers with the lowest viral loads (elite controllers) and were rarely detected among noncontrollers, supporting a relationship between HIV-specific T-cell proliferation and viral control. CONCLUSIONS: Collectively, these data suggest a model in which HIV controllers maintain low levels of viral replication through robust HIV-specific T-cell responses in an environment of low inflammation and reduced availability of activated target cells.

The purpose of this study was to increase awareness, gain insight into acquisition, and assess the virulence of the hypervirulent (hypermucoviscous) clinical variant (hvKP) that is entrenched in the Pacific Rim but emerging in Western countries. A case of community-acquired liver abscess with metastatic spread to the spleen is described. Comparative in vitro and in vivo virulence studies on this isolate (hvKP1) and four randomly chosen blood isolates of "classic" K. pneumonia strains (cKP1-4) were performed. Cases of hvKP infection are occurring in Western countries and are under-recognized. A hypermucoviscous phenotype is a surrogate laboratory marker for this variant. The propensity of hvKP strains for metastatic spread in non-compromised hosts is both a defining and unusual trait. The mode of acquisition in the described case was unclear but potential means are discussed. hvKP1 was more resistant to complement and neutrophil-mediated bactericidal activity and was more virulent in a rat subcutaneous abscess model than cKP1-4. Recognition of the hypermucoviscous phenotype, defined by a positive "string-test", will alert the microbiologist or clinician that the infecting strain may be a hvKP, which is hypervirulent compared to cKP. This will improve our understanding of the epidemiology and clinical spectrum of infection, which may be more extensive than appreciated.

RATIONALE: Quantitation and determination of antigen specificity of systemic and mucosal immune responses to influenza vaccination is beneficial for future vaccine development. Previous methods to acquire this information were costly, time consuming and sample exhaustive. The benefits of suspension microbead array (MBA) analysis are numerous. The multiplex capabilities of the system conserve time, money and sample, while generating statistically powerful data.OBJECTIVE: To demonstrate the use of the assay by comparing the humoral influenza-specific responses of two cohorts from two countries that differed in circulating influenza strains and rates of influenza vaccination.METHODS: Influenza hemagglutinin (HA) from different strains were coated on microbeads and incubated with serum samples to capture immunoglobulin (Ig) A1and IgG1host antibodies.RESULTS: Statistically significant differences in IgA1and IgG1exist between the serum samples from Winnipeg (Manitoba) donors and those from Kenyan (Africa) donors. Data were compared using Mann-Whitney nonparametric tests. The Winnipeg donors had higher mean fluorescence intensity values, with significant P values for anti-HA IgA1to A/Wyoming/3/2003 (P=0.044), A/Vietnam/1203/2004 (P=0.0179), A/New Caledonia/20/99 (P1to A/Wyoming/3/2003 (P=0.0135), B/Tokyo/53/99 (P=0.006) and B/Jilin20/2003 (P=0.026).CONCLUSION: Influenza-specific IgA1and IgG1antibodies were successfully detected using MBA technology. A significant difference in antibody response was observed between Winnipeg and Kenyan donor serums. MBA analysis is a relatively quick and cost-effective method for serum antibody analysis. The potential to simultaneously assay small sample volumes for a multitude of antigens makes this method invaluable for future vaccine response monitoring.

Influenza vaccine provides protection against infection with matched strains, and this protection correlates with serum antibody titres. In addition to antibodies, influenza-specific CD8+ T-lymphocyte responses are important in decreasing disease severity and facilitating viral clearance. Because this response is directed at internal, relatively conserved antigens, it affords some cross-protection within a given subtype of influenza virus. With the possibility of a broader A(H1N1) Mexico outbreak in the fall of 2009, it appeared worthwhile studying the degree of cellular immune response-mediated cross-reactivity among influenza virus isolates. The composition of the 2006–2007 influenza vaccine included the A/New Caledonia/20/1999 strain (comprising a virus that has been circulating, and was included in vaccine preparations, for 6–7 years) and two strains not previously included (Wisconsin and Malaysia). This combination afforded us the opportunity to determine the degree of cross-reactive cellular immunity after exposure to new viral strains. We analysed the antibody responses and the phenotype and function of the T cell response to vaccine components. The results obtained show that antibody responses to A/New-Caledonia were already high and vaccination did not increase antibody or cytotoxic T lymphocyte responses. These data suggest that repeated exposure to the same influenza stain results in limited boosting of humoral and cellular immune responses.

Regulatory T cells, a subset of CD4(+) T lymphocytes, play a pivotal role in the maintenance of the balance between the tissue-damaging and protective effects of the immune response. These cells have immunosuppressive function and have been intensely studied in the context of autoimmunity, cancer, allergies, asthma, and infectious diseases. Their role in chronic and persistent viral infections is well appreciated. In acute viral infections, the function of these cells is still unclear. The host and pathogen factors that control the generation and activity of regulatory T cells and the role of these cells in modulating expansion, contraction, and development of immune memory in acute respiratory virus infection need to be further elucidated.

The epidemiology of infective endocarditis is changing. The combination of increased life-expectancy, the burden of chronic disease, immunosuppression as a result of improving treatment and prognosis of malignancies and transplantation and the increasing device-related and iatrogenic infections have resulted in risk factors for infectious endocarditis. The etiological agents vary according to the underlying predisposing factors with increases in resistant health-care associated infections among the special populations reviewed in this chapter.

Klebsiella pneumoniae (Kp) is an important pathogen both in the community and the hospital setting. In the community the emergence of virulent organisms with predominantly K1/K2 capsular serotypes has been observed over the last 20 years, these pathogens cause a distinct clinical syndrome consisting of pyogenic liver abscesses, sometimes accompanied by meningitis and abscesses elsewhere. In the hospital environment, under heavy antibiotic usage, multiple drug resistance has been increasingly observed in Kp. Kp strains harbouring extended spectrum beta-lactamases (ESBL) and more recently metallocarbapenemase, conferring resistance to many of the antibiotics available, have been described in many parts of the world. These multi-drug-resistant organisms are affecting the choice of antimicrobial therapy, are a major cause for increasing hospital costs and duration of hospitalisations. Some of the ESBL-producing Kp have already moved into the community and are creating therapeutic problems in a setting where empiric, oral antimicrobial therapy is a common practice. In this review we will discuss these two Kp emerging trends.

Host response biomarkers can accurately distinguish between influenza and bacterial infection. However, published biomarkers require the measurement of many genes, thereby making it difficult to implement them in clinical practice. This study aims to identify a single-gene biomarker with a high diagnostic accuracy equivalent to multi-gene biomarkers.In this study, we combined an integrated genomic analysis of 1071 individuals with

Bartonella spp are important causes of culture-negative endocarditis, generally causing a subacute insidious form of endocarditis, often leading to a delay in diagnosis. Most patients have fever and often present with signs and symptoms of heart failure. The diagnosis is frequently established only on meticulous examination of the resected heart valve with the polymerase chain reaction technique. We present a case of B quintana mitral and aortic valve endocarditis with associated severe valvular insufficiency and decompensated heart failure precipitated by Streptococcus pneumoniae bacteremia, necessitating urgent surgical valve replacement. Pathologic examination of the valve complemented by serologic and molecular testing established the surprising diagnosis of B quintana endocarditis.

Human immunodeficiency virus type 1 (HIV-1) infection is associated with variable rates of disease progression, influenced by the quality of CD8 T-lymphocyte response, which is determined by human leukocyte antigen (HLA) I alleles. Some individuals progress slowly and maintain viral control, while at the opposite end of the spectrum some individuals endure a faster progression with rapid CD4 decline. We sought to determine the role of HLA-B allele frequency on rapid HIV disease progression. It was hypothesized that rapid progression is associated with the presence of high allele frequency of HLA-B35 and HLA-B homozygocity.This retrospective cohort study was conducted in the Manitoba HIV Program, Health Sciences Centre, a tertiary care facility in Winnipeg, Manitoba, Canada. We defined a set of new criteria to describe a subset of individuals with the most rapid HIV disease progression, and collected demographic, clinical, laboratory (CD4 count, viral load) and HLA data on a subset of 20 individuals meeting these criteria.Among those individuals who display extreme rapid progression, an overrepresentation of Aboriginal ethnicities, high frequencies of HLA-B35 and significantly higher rates of HLA-B51, as well as a very high rate of homozygocity for HLA-B alleles, were observed.Individuals with the most rapid disease progression have higher rates of HLA-B homozygocity, HLA-B51 alleles and higher viral loads than those with normal progression rates. This group, at the extreme end of the spectrum of progression, should be targeted for early treatment.