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Prior studies have shown that HIV patients develop permanent pulmonary dysfunction following an episode of community-acquired pneumonia (CAP). However, the mechanism causing pulmonary dysfunction remains an enigma. HIV patients experience chronic inflammation. We hypothesized that CAP exacerbates inflammation in HIV patients resulting in an accelerated decline in lung function. A prospective cohort pilot study enrolled HIV patients hospitalized in Medellin, Colombia, with a diagnosis of CAP. Sixteen patients were eligible for the study; they were split into 2 groups: HIV and HIV+CAP. Plasma, sputum, and pulmonary function test (PFT) measurements were retrieved within 48 h of hospital admission and at 1 month follow-up. The concentrations of 13 molecules and PFT values were compared between the 2 cohorts. The HIV+CAP group had lower lung function compared to the HIV group; forced vital capacity (FVC)% predicted and forced expiratory volume in 1 s (FEV

Due to poor diagnostics and increased co-infections, HIV-associated Legionella infections are underreported. We aimed to retrospectively determine the frequency of Legionella infections in bronchoalveolar lavage (BAL) from HIV-associated pneumonia patients hospitalized in Medellin, Colombia, between February 2007 and April 2014. Although culture was negative, 17 BAL (36%) were positive for Legionella by quantitative polymerase chain reaction, most of which were in the Mycobacterium tuberculosis or Pneumocystis jirovecii co-infected patients, and included L. anisa (n = 6), L. bozemanae (n = 4), L. pneumophila (n = 3), and L. micdadei (n = 2). All L. bozemanae and L. micdadei associated with Pneumocystis, while all L. pneumophila associated with M. tuberculosis. Legionella probable cases had more complications and higher mortality rates (P = 0.02) and were rarely administered empirical anti-Legionella therapy while in hospital. Clinicians should be aware of the possible presence of Legionella in HIV and M. tuberculosis or P. jirovecii co-infected patients.

BackgroundA cohort study was conducted to describe and compare the characteristics of SARS-CoV-2 infection in hospitalized children in three countries.MethodsThis was a retrospective cohort of consecutive children admitted to 15 hospitals (13 in Canada and one each in Iran and Costa Rica) up to November 16, 2020. Cases were included if they had SARS-CoV-2 infection or multi-system inflammatory syndrome in children (MIS-C) with molecular detection of SARS-CoV-2 or positive SARS-CoV-2 serology.ResultsOf 211 included cases (Canada N=95; Costa Rica N=84; Iran N=32), 103 (49%) had a presumptive diagnosis of COVID-19 or MIS-C at admission while 108 (51%) were admitted with other diagnoses. Twenty-one (10%) of 211 met criteria for MIS-C. Eighty-seven (41%) had comorbidities. Children admitted in Canada were older than those admitted to non-Canadian sites (median 4.1 versus 2.2 years; pConclusionsApproximately half of hospitalized children with confirmed SARS-CoV-2 infection or MIS-C were admitted with other suspected diagnoses. Disease severity was higher at non-Canadian sites. Neonates, children with comorbidities and those with chest radiographs compatible with COVID-19 were at increased risk for severe or critical COVID-19.Main pointsApproximately half of hospitalized children with laboratory confirmed MIS-C or SARS-CoV-2 infection were admitted with another primary diagnoses. The severity of disease was higher in the middle income countries (Costa Rica and Iran) than in Canada.

Introduction Despite the life-prolonging effects of Highly Active Antiretroviral Therapy (HAART), persons with HIV are still prone to higher rates of non-AIDS related morbidity (such as heart, kidney, and liver disease) than the general public. This is likely due to chronic immune activation and inflammation that persists in HIV-positive persons despite virological suppression. What remains undetermined, however, is whether a link exists between chronic inflammation/immune activation and suboptimal immune recovery on HAART. The hypothesis of the present study is that higher levels of systemic subclinical inflammation and immune activation are linked with suboptimal immune recovery on HAART. Methods Fifteen eligible patients from the Manitoba HIV program were enrolled and followed for up to two years; blood samples were drawn at 4 timepoints each, and concentrations of 21 proinflammatory markers were measured. Patients were grouped according to CD4:CD8 recovery at viral suppression, and the inflammatory profiles of the two groups were compared. Results and conclusions APRIL and BAFF are higher in those with poor recovery at the point of viral suppression, but were also higher in this group at the onset of therapy and through the three additional follow-up visits. TNF-R1, CD163, and Osteopontin, were also in higher concentrations at the outset of therapy and beyond. These five molecules could thus see potential use in the future as biomarkers of likely poor immune recovery. Future work should focus on replicating these findings with larger cohorts.

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.

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.

Summary Background Environmental surfaces have long been suspected to be a reservoir that could contribute to the presence of micro-organisms in healthcare facilities. The objective of this study was to evaluate the effect of providing weekly feedback to the housekeeping staff in improving and sustaining cleaning compliance when using ultraviolet visible marker (UVM) as an audit tool. Methods The housekeeping staff selected 90% as the cleaning compliance target. The UVM was applied to the toilet seat, sink, soap dispenser and door knob surfaces within the patient's washrooms on consecutive weekdays. The study included three arms: staff in arm 1 received cleaning compliance feedback throughout the 24-week study period, arm 2 and arm 3 staff received feedback for weeks 13–24 and weeks 1–12, respectively. Feedback was also provided to housekeeping staff by posting graphs on the wards and in the housekeeping office. Findings A pre-study audit showed 66.9%, 66.5% and 66.4% cleaning compliance for arms 1, 2 and 3 respectively. While receiving weekly feedback, all three arms demonstrated significantly improved cleaning compliance (86.7%, 80.4% and 73.7% for arms 1, 2 and 3, respectively). The use of casual staff may have contributed to difficulty in achieving better cleaning compliance as arms 1, 2 and 3 had 16.1%, 26% and 40.3% of shifts filled by casual staff, respectively. Conclusions The use of UVM as an audit tool combined with weekly feedback of results to housekeeping staff resulted in significant, sustained improvement in the overall level of cleaning compliance of housekeeping staff.

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.

Reported in this study is the successful incorporation of a hydrophilic antibiotic drug, tetracycline hydrochloride (TCH), into electrospun PEG–PLA nanofibrous membrane without loss of its bioactivity. Degradation behavior of the copolymer was studied in vitro. Release behavior of TCH from the electrospun membrane and antimicrobial effects of the TCH-loaded membrane against Staphylococcus aureus culture were investigated. The medicated nanofibrous membrane demonstrated sustained release of TCH over 6 days and was found to be effective in inhibiting growth of S. aureus. In addition, increasing the antibiotic drug content in the electrospun membranes was found to enhance the anti-bacterial effectiveness of the medicated fiber mats. And the combination of mechanical barriers provided by the electrospun biodegradable nanofibrous membranes and their capability of local sustained delivery of antibiotics made these membranes more useful in biomedical applications, particularly as new wound dressings for ulcers caused by diabetes or other diseases, and to provide a better means of treatment for these malignant wounds and ulcers. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010

Background Environmental surfaces in health care facilities contaminated with Clostridium difficile spores can be a reservoir that contribute to transmission of hospital-acquired infections. Microfiber cleaning cloths may improve the effectiveness of surface cleaning. The objective of this study was to assess the removal and transfer of C difficile spores on surfaces cleaned by microfiber compared with cotton cloths. Methods C difficile spores (approximately 4.2 log 10 /site) were applied to ceramic surfaces. Microfiber or cotton cloths were used to wipe the surfaces that were sprayed with either buffer or a nonsporicidal cleaning agent. To ensure reproducible pressure and surface contact time, a drill apparatus was used. The pressure was 1.5-1.77 N, and the total number of rotations was 10. Viable counts were used to assess the efficiency of microfiber and cotton cloths in removing and transferring spores. Results Of 4.4 log 10 C difficile spores inoculated on a ceramic surface, microfiber and cotton cloths removed 2.4 and 1.7 log 10 , respectively. Microfiber cloths containing 4.2 log 10 C difficile spores transferred 1.7 log 10 C difficile spores when used to wipe a ceramic surface compared with cotton cloths that transferred 2.4 log 10 . Similarly microfiber wipes transferred fewer spores on consecutive surfaces wiped compared with cotton cloths (0.8 log 10 vs 1.80 log 10 ). Conclusion The use of microfiber cloths may reduce the risk of C difficile spore transfer during surface cleaning.

Background Due to the lack of clinical suspicion, poor diagnostic performance, increased patient immunosuppression, and the increased chance of co-infection, HIV-associated Legionella community-acquired pneumonia (CAP) is currently under-reported. Thus, this study aimed to determine the frequency of Legionella in CAP-infected HIV patients. Methods Following initial diagnosis, DNA extracted from bronchoalveolar lavage (BAL) from CAP-infected HIV patients hospitalized at Hospital San Vicente Fundación in Medellin, Colombia were assayed for the presence of Legionella species (PAN Legionella, L. Anisa, L. bozemanii, L. micdadei, L. pneumophila and L. pneumophila serogroup 1) using singleplex real-time PCR (qPCR). Results were validated with agarose gel electrophoresis and reconfirmed using pre-amplification qPCR. Results Of the 59 HIV-infected individuals in the study, majority were non-smokers (64.4%), male (77.9%), and highly immunosuppressed (CD4 cell count

RESUMEN: Queríamos investigar el perfil de citoquinas pro-inflamatorias / quimiocinas asociados con los agentes etiológicos identificados en pacientes con VIH. Los pacientes inmunodeprimidos ingresados ​​en dos hospitales en Medellín, Colombia, con diagnóstico clínico y radiográfico de la neumonía se inscribieron en el estudio. Después de la autorización, se recogió el lavado broncoalveolar (BAL) para bacterias, micobacterias y hongos diagnóstico. Todos los pacientes fueron seguidos durante un año. Una muestra de BAL almacenada se utiliza para la detección de citoquinas / quimioquinas y citoquinas medida usando ensayos comerciales humana, basados ​​en perlas magnéticas 19-plex. El análisis estadístico se realizó mediante la asignación de niveles de concentraciones de citoquinas / quimioquinas en 75 percentil (superior). Se llevaron a cabo análisis de componentes principales (PCA) y el análisis de Kruskal-Wallis para identificar la agrupación de citoquinas con las diversas etiologías infecciosas (hongos, Mycobacterium tuberculosis - BTT, y bacterias). La edad promedio de los pacientes era de 35 años, de los cuales el 77% eran hombres, y la mediana del recuento de CD4 de 33cells / l. De los 57 pacientes infectados por el VIH, la mortalidad hospitalaria fue del 12,3% y el 33% murió dentro de un año de seguimiento. El PCA reveló aumento de IL-10, IL-12, IL-13, IL-17, eotaxina, GCSF, MIP-1α, y las concentraciones de MIP-1 beta que se asocia con la infección MTB. En los pacientes con infección fúngica probada, bajas concentraciones de IL-1RA, IL-8, se identificaron TNF-α y VEGF. Las infecciones bacterianas muestran un patrón de citoquinas distintas y no fueron mal clasificados utilizando los patrones de citoquinas MTB u hongos (valor de p 75 percentile (higher). Principal component analysis (PCA) and Kruskal-Wallis analysis were conducted to identify the clustering of cytokines with the various infectious etiologies (fungi, Mycobacterium tuberculosis - MTB, and bacteria). Average age of patients was 35, of whom 77% were male, and the median CD4 count of 33cells/μl. Of the 57 HIV infected patients, in-hospital mortality was 12.3% and 33% died within a year of follow up. The PCA revealed increased IL-10, IL-12, IL-13, IL-17, Eotaxin, GCSF, MIP-1α, and MIP-1β concentrations to be associated with MTB infection. In patients with proven fungal infection, low concentrations of IL-1RA, IL-8, TNF-α and VEGF were identified. Bacterial infections displayed a distinct cytokine pattern and were not misclassified using the MTB or fungi cytokine patterns (p-value

Blastomycosis is an uncommon endemic fungal infection. It is presumed that in the endemic regions, the number of exposed individuals is significantly greater than those in whom clinical manifestations develop. We conducted a case-control study of individuals with clinical blastomycosis and controls with similar exposure but who did not develop disease. A genetic association was observed between the Gc-2 allele of vitamin D binding protein and reduced susceptibility to blastomycosis in a Canadian cohort. The Gc-2 allele can affect increased antimicrobial activity of macrophages. It may be possible to mimic this mechanism of protection by vitamin D supplementation.