Search

International audience; Background - The impact of early valve surgery (EVS) on the outcome of Staphylococcus aureus (SA) prosthetic valve infective endocarditis (PVIE) is unresolved. The objective of this study was to evaluate the association between EVS, performed within the first 60 days of hospitalization, and outcome of SA PVIE within the International Collaboration on Endocarditis-Prospective Cohort Study. Methods - Participants were enrolled between June 2000 and December 2006. Cox proportional hazards modeling that included surgery as a time-dependent covariate and propensity adjustment for likelihood to receive cardiac surgery was used to evaluate the impact of EVS and 1-year all-cause mortality on patients with definite left-sided S. aureus PVIE and no history of injection drug use. Results - EVS was performed in 74 of the 168 (44.3%) patients. One-year mortality was significantly higher among patients with S. aureus PVIE than in patients with non-S. aureus PVIE (48.2% vs 32.9%; P = .003). Staphylococcus aureus PVIE patients who underwent EVS had a significantly lower 1-year mortality rate (33.8% vs 59.1%; P = .001). In multivariate, propensity-adjusted models, EVS was not associated with 1-year mortality (risk ratio, 0.67 [95% confidence interval, .39-1.15]; P = .15). Conclusions - In this prospective, multinational cohort of patients with S. aureus PVIE, EVS was not associated with reduced 1-year mortality. The decision to pursue EVS should be individualized for each patient, based upon infection-specific characteristics rather than solely upon the microbiology of the infection causing PVIE.

Summary Commercial air travel is widespread, with close to 2 billion people traveling each year. The association between venous thromboembolism (VTE) and confined sitting has been established and a correlation between the distance traveled and its incidence had been documented. Most studies underscore stasis caused by immobility as the cause of VTE and ignore the possible contribution of additional factors including coagulation and the blood vessel wall. Recent studies indicate that hypobaric hypoxia may contribute to blood vessel wall alteration and activation of coagulation. We suggest that air travel associated hypobaric hypoxia may lead to endothelial injury and initiation of a procoagulatory response, effects which are augmented by the reoxygenation upon landing, thus culminating in thrombosis. Prevention of air travel associated hypoxia and reoxygenation injury may decrease the incidence of flight associated VTE.

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

Background— Use of surgery for the treatment of infective endocarditis (IE) as related to surgical indications and operative risk for mortality has not been well defined. Methods and Results— The International Collaboration on Endocarditis–PLUS (ICE-PLUS) is a prospective cohort of consecutively enrolled patients with definite IE from 29 centers in 16 countries. We included patients from ICE-PLUS with definite left-sided, non–cardiac device–related IE who were enrolled between September 1, 2008, and December 31, 2012. A total of 1296 patients with left-sided IE were included. Surgical treatment was performed in 57% of the overall cohort and in 76% of patients with a surgical indication. Reasons for nonsurgical treatment included poor prognosis (33.7%), hemodynamic instability (19.8%), death before surgery (23.3%), stroke (22.7%), and sepsis (21%). Among patients with a surgical indication, surgical treatment was independently associated with the presence of severe aortic regurgitation, abscess, embolization before surgical treatment, and transfer from an outside hospital. Variables associated with nonsurgical treatment were a history of moderate/severe liver disease, stroke before surgical decision, and Staphyloccus aureus etiology. The integration of surgical indication, Society of Thoracic Surgeons IE score, and use of surgery was associated with 6-month survival in IE. Conclusions— Surgical decision making in IE is largely consistent with established guidelines, although nearly one quarter of patients with surgical indications do not undergo surgery. Operative risk assessment by Society of Thoracic Surgeons IE score provides prognostic information for survival beyond the operative period. S aureus IE was significantly associated with nonsurgical management.

Underwater hearing acuity and sound localization are improved by the presence of an air interface around the pinnae and inside the external ear canals.Hearing threshold and the ability to localize sound sources are reduced underwater. The resonance frequency of the external ear is lowered when the external ear canal is filled with water, and the impedance-matching ability of the middle ear is significantly reduced due to elevation of the ambient pressure, the water-mass load on the tympanic membrane, and the addition of a fluid-air interface during submersion. Sound lateralization on land is largely explained by the mechanisms of interaural intensity differences and interaural temporal or phase differences. During submersion, these differences are largely lost due to the increase in underwater sound velocity and cancellation of the head's acoustic shadow effect because of the similarity between the impedance of the skull and the surrounding water.Ten scuba divers wearing a regular opaque face mask or an opaque ProEar 2000 (Safe Dive, Ltd., Hofit, Israel) mask that enables the presence of air at ambient pressure in and around the ear made a dive to a depth of 3 m in the open sea. Four underwater speakers arranged on the horizontal plane at 90-degree intervals and at a distance of 5 m from the diver were used for testing pure-tone hearing thresholds (PTHT), the reception threshold for the recorded sound of a rubber-boat engine, and sound localization. For sound localization, the sound of the rubber boat's engine was randomly delivered by one speaker at a time at 40 dB HL above the recorded sound of a rubber-boat engine, and the diver was asked to point to the sound source. The azimuth was measured by the diver's companion using a navigation board.Underwater PTHT with both masks were significantly higher for frequencies of 250 to 6000 Hz when compared with the thresholds on land (p0.0001). No differences were found in the PTHT or the reception threshold for the recorded sound of a rubber-boat engine for dry or wet ear conditions. There was no difference in the sound localization error between the regular mask and the ProEar 2000 mask.The presence of air around the pinna and inside the external ear canal did not improve underwater hearing sensitivity or sound localization. These results support the argument that bone conduction plays the main role in underwater hearing.

A short course of antimicrobial therapy should be the aim of all treatment unless otherwise indicated. Factors allowing short treatment courses are those that depend on the host, on the infection and on the agents administered. In essence, immunodeficiencies, long-standing infections, abscesses, or infections associated with foreign bodies cannot be treated with short-course therapies. Bactericidal antibiotics are the only agents suitable for short-course therapy. Many severe infections such as primary bacteraemia and bacteraemia complicating pneumonia, acute pyelonephritis and meningitis are amendable to short-course therapy, whilst others are not. The benefits of short-duration therapy are obvious and may contribute to halting resistance, reduced costs and rational patient management.

Background: Acute pulmonary edema has been noted in swimmers and divers, and has been termed swimming-induced pulmonary edema (SIPE). The mechanisms and consequences of SIPE are unknown, and there are currently no series of carefully evaluated patients with this condition. Herein we report the clinical presentation, incidence of recurrence, findings on physical examination, chest radiography, and oxygen saturation in 70 trainees with a diagnosis of SIPE. We also report the results of forced spirometry in a subgroup of 37 swimmers. Methods: SIPE was diagnosed when severe shortness of breath and cough were reported during or after swimming, and were associated with evidence of pulmonary edema. During the years from 1998 to 2001, 70 cases of SIPE were documented in young healthy male subjects participating in a fitness-training program. Physical examination and pulse oximetry were performed immediately. Chest radiographs were obtained in all cases 12 to 18 h following onset of symptoms. In 37 swimmers, spirometry was performed at the time of chest radiography and again after 7 days. Results: All subjects complained of severe shortness of breath. Sixty-seven of the 70 subjects (95.7%) had a prominent cough; in 63 subjects (90%), there was significant sputum production. Hemoptysis was observed in 39 subjects (55.7%). Mean arterial oxygen saturation after swimming was 88.4 ± 6.6% breathing air, compared with 98 ± 1.7% breathing air at rest before the start of the swimming trial (mean ± SD) [p Conclusions: In our trainee population, SIPE is a not uncommon, often recurrent phenomenon that significantly influences performance. It is not clear what predisposes to its occurrence or recurrence and what, if any, are its long-term effects.

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 in vitro experiments using well-established infection models.We identified a single-gene biomarker, IFI27, which had a high prediction accuracy (91%) equivalent to that obtained by multi-gene biomarkers. In vitro studies showed that IFI27 was upregulated by TLR7 in plasmacytoid dendritic cells, antigen-presenting cells that responded to influenza virus rather than bacteria. In vivo studies confirmed that IFI27 was expressed in influenza patients but not in bacterial infection, as demonstrated in multiple patient cohorts (n=521). In a large prospective study (n=439) of patients presented with undifferentiated respiratory illness (aetiologies included viral, bacterial and non-infectious conditions), IFI27 displayed 88% diagnostic accuracy (AUC) and 90% specificity in discriminating between influenza and bacterial infections.IFI27 represents a significant step forward in overcoming a translational barrier in applying genomic assay in clinical setting; its implementation may improve the diagnosis and management of respiratory infection.

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.

Setting: Two prisons in Medellín and Itagüí, Colombia. Objective: To determine the prevalence of tuberculin skin test (TST) positivity in prisoners and the annual risk of tuberculous infection (ARTI), to identify risk factors associated with a positive result, and to describe progression to active disease. Design: Cross-sectional study. Inmates were included if time of incarceration was ⩾1 year and excluded if subjects had had previous or active tuberculosis (TB), or conditions that could hamper TST administration or interpretation. Results: We screened 1014 inmates. The overall prevalence of TST positivity was 77.6%. The first TST administration resulted in 66% positivity, and the second TST an additional 11.6%. In Prison One, the ARTI was 5.09% in high TB incidence cell blocks and 2.72% in low TB incidence blocks. In Prison Two, the ARTI was 2.77%. Risk factors associated with TST positivity were history of previous incarceration and length of incarceration. Among all those included in the study, four individuals developed active pulmonary TB. Conclusion: Prevalence of TST positivity in prisoners and the ARTI were higher than in the general population, but differed between prisons; it is important to apply a second TST to avoid an overestimation of converters during follow-up. COL0003249 COL0004362 COL0126131

Background. Hypermucoviscous Klebsiellapneumoniae (HMVKP) emerged as a cause of invasive infections in South-East (SE) Asia. It has become the most common cause of liver abscess in that region, and it is a significant causative organism in endogenous endophthalmitis and meningitis. During the past decade, cases of this uniquely virulent organism have been reported outside of SE Asia, with a propensity to affect individuals of SE Asian descent. Cases have been reported from North America including Canada. Methods. We report a case of a patient of Filipino descent living in Canada who presented with recurrent HMVKP bacteremia in the absence of pyogenic liver abscess or other localized metastatic Klebsiella infection. Results. Investigations identified an immunoglobulin (Ig)G2 deficiency and low IgM indicating potential common variable immunodeficiency, and administration of intravenous immunoglobulins was associated with prevention of further recurrences. Conclusions. To our knowledge, this is the first report of HMVKP associated with predisposing antibody deficiency.

Infective endocarditis has many facets and various expressions depending on the site of infection, microorganism, underlying heart lesion, immune status of the host, and remote effects such as emboli, organ dysfunction, and the condition of the host. Diagnosis depends on meticulous clinical examination, blood cultures results, and echocardiographic findings. The management of the patient with endocarditis in the intensive care unit is complex and needs a multidisciplinary team, including an intensivist, cardiologist, experienced echocardiologist, infectious diseases specialist, and cardiac surgeon. The medical and surgical management of such patients is complex, and timely decisions are important.

Vancomycin-resistant enterococci (VRE) consist mainly of Enterococcus faecalis and E faecium, the latter mostly hospital-acquired. In addition, E gallinarum and E casseliflavus are intrinsically vancomycin-resistant and are community-acquired. VRE have become common in many hospitals throughout the world and, once established, are very difficult to eradicate. VRE are difficult to treat; therefore, infection control measures in hospitals are of prime importance in preventing the establishment of these pathogens. Most severe VRE infections will need combination therapy because many of the effective antimicrobial agents, when used alone, have only a bacteriostatic effect.

Clinical trials are traditionally designed by pharmaceutical companies or clinical research organizations to address the requirements and regulations of national regulatory agencies such as the US Food and Drug Administration. The criteria for enrolment are strict and well-defined, necessitating the screening of large numbers of individuals for each subject enrolled. Common exclusion criteria include extremes of age and weight, pregnancy, previous treatment with effective antibiotics for the same infection, organ dysfunction, malignant diseases with a short survival time, advanced HIV etc. In clinical trials, cost, length of hospital stay, complexity of drug administration and patient and family preferences are rarely considered, and seldom make their way into the report of the trial. The limited patient population and under-representation of sicker, older individuals leads to underestimation of drug toxicity and overestimation of efficacy. Postmarketing studies are commonly used to document adverse reactions, but they are not supported by industry and receive limited funding. We chose to evaluate the applicability to general staphylococcal bacteraemia patient populations of clinical trials comparing antimicrobial agents used to treat Staphylococcus aureus bacteraemia.

Introduction Endogenous endophthalmitis is uncommon, accounting for 5% to 10% of endophthalmitis cases. It is caused by hematogenous seeding of the intraocular tissues by fungi or bacteria. The retina, choroid, and ciliary body are the primary intraophthalmic sites of infection due to a higher blood fl ow to these structures. An uncommon but devastating infection, endophthalmitis frequently results in total visual loss or severe compromise of visual fi elds and visual acuity. Endophthalmitis commonly affects persons with comorbidities such as immunosuppression, neutropenia, organ transplant, intravenous drug use, indwelling vascular catheter, parenteral alimentation, diabetes mellitus, and hemodialysis [ 1 , 2 ]. Offending organisms include fungi and gram-positive and gram-negative bacteria. The more commonly associated agents are Staphylococcus aureus, Streptococcus pneumoniae, Listeria monocytogenes, Bacillus cereus, Pseudomonas aeruginosa, Escherichia coli, Salmonella spp, Neisseria meningitidis , and Klebsiella pneumoniae . Although the proportion of gram-negative and gram-positive organisms has not changed in recent decades, an increase in the incidence of K. pneumoniae has been observed, predominantly in Southeast Asia. The following case illustrates the salient features of hypermucoviscous K. pneumoniae (HMVKp) endophthalmitis. A previously healthy 63-year-old Filipino male presented with abdominal discomfort. Klebsiella bacteremia was diagnosed. Abdominal CT scan showed a liver cyst measuring 4 cm, which was interpreted as a benign liver cyst. The patient received a 14-day course of cefotaxime and was discharged. Forty-eight hours after discharge, he reported worsening left eye pain, which was diagnosed as endophthalmitis, and underwent urgent vitrectomy. Culture of vitreous humor grew K. pneumoniae . Two weeks later he returned with recurrent abdominal pain, weight loss of 35 pounds, and low-grade fever. Investigations revealed a liver cyst and pericardial effusion. Subsequently, clinical signs of tamponade developed; pericardiocentesis yielded a grossly purulent fl uid from which K. pneumoniae was isolated. The salient features of this emerging clinical entity include the relative absence of comorbidities, the presence of K. pneumoniae bacteremia, liver abscess, and metastatic complications, among which endophthalmitis and meningitis are the most commonly reported.

Old world cutaneous leishmaniasis (CL) is caused byLeishmania majorandLeishmania tropica,and is endemic to several Asian and Middle-Eastern countries where the rates of infection can be substantial. CL is one of the most common vector-transmitted parasitic infections in Afghanistan. Six cases of CL in Canadian soldiers returning from Afghanistan are reported in the present study. Their lesions did not improve with fluconazole therapy, and the organism demonstrated in vitro resistance. Oral miltefosine seemed effective.

Currently, the treatment of sudden deafness (SD) is based mainly on complete bed rest and the administration of corticosteroids. Hyperbaric oxygen therapy (HBOT) has previously been suggested as adjunctive treatment. We describe two cases of successful HBOT for SD. The first patient presented with moderate mid-frequency hearing loss without accompanying symptoms, whereas the second patient had moderate low-frequency hearing loss with persistent tinnitus and a single episode of vertigo. HBOT in addition to conventional treatment soon after diagnosis resulted in full recovery of hearing in both patients. The pathogenesis of SD may involve a reduction in cochlear blood flow and perilymph oxygenation, making early HBOT a reasonable treatment modality for this condition.

Community-acquired primary pyogenic liver abscess (PLA) caused by Klebsiella pneumoniae is an emerging infectious entity, with cases reported in the scientific literature over the past 15 y mainly from Taiwan and Asia, but also from Europe and North America. We describe a case of PLA caused by the hypermucoviscous, K1 capsular serotype of Klebsiella pneumoniae in a Canadian man and highlight the unique features of this increasingly common cause of liver abscess.

Bilateral vision loss during hemodialysis is a rare but devastating entity, with grim prognosis for sight. The etiologies are diverse but share ischemia as a common mechanism. This is a report of a patient with bilateral sight loss during hemodialysis, with early hyperbaric treatment and return of visual acuity to baseline. Hyperbaric treatment should be considered, where early administration is possible, for bilateral blindness during hemodialysis.

Staphylococcus aureus and methicillin-resistant S aureus have emerged as the most important nosocomial pathogens. Traditional therapy may be sufficient in most but not all patients, in whom alternatives should be sought. The infection is often complicated with several sites of metastatic foci and is nosocomial frequently. New antibiotics to fight MRSA have been introduced and are equivalent or better than vancomycin.

We describe a case of severe pneumonia caused by Legionella pneumophila serotype 1 in a woman receiving the tumor necrosis factor–α antagonist to treat rheumatoid arthritis. As use of tumor necrosis factor–α inhibitors increase, clinicians should consider their possible association with legionellosis.

The present report describes a case of chronic diarrhea with several ulcers in the ascending colon in a 47-year old woman who immigrated to Canada from the Philippines. A biopsy from affected colon revealed caseating granulomas and culture grew mycobacterium avium subspecies. Polymerase chain reaction from the colonic biopsy specimen confirmed the presence of mycobacterium avium subspecies that was subsequently identified by hsp65 sequence to be mycobacterium avium hominissuis (MAH). Anti-mycobacterial therapy was started but discontinued by the patient. After 6 months a repeat colonoscopy was macroscopically normal and no granulomas could be seen on biopsies taken from normal appearing colonic tissue. The epidemiological features, host-range and laboratory identification of this unusual organism are discussed.

A substantial proportion of patients treated for early syphilis have serofast nontreponemal titers after therapy. Serological cure at 6 months is associated with age, number of sexual partners, Jarisch-Herxheimer reaction, and an interaction between syphilis stage and baseline nontreponemal titers.

Background: Maraviroc is an allosteric, non-competitive blocker of CCR5, interfering with its ability to bind to the HIV GP120 and thus preventing HIV cell entry. CCR5 is involved in recruiting immune cells to sites of viral invasion in the respiratory tract. This postulated role of CCR5 led us to perform a meta-analysis of the largest clinical drug trials that evaluated CCR5 antagonists, as part of antiretroviral regimens, with focus on the occurrence of respiratory infections in general and viral infections in particular in CCR5 antagonist recipients. Data source and eligibility criteria: Clinical trials involving administration of Maraviroc to HIV infected individuals were reviewed with emphasis on reported respiratory infections. We included in the analysis those studies enrolling more than 100 participants in the maraviroc treatment arm. Results: We compared individuals treated with optimized background regimen plus placebo to those receiving the background regimen along with the CCR5 anatagonist maraviroc. We found in the clinical data significantly more respiratory infections in the CCR5 blocker treated arm than in the control arm. Limitations: The studies had limited microbiological analysis of respiratory infections and the categorization differs between the studies included. Conclusions: This observation suggests that the CCR5 blockade may lead to more infections caused by other viruses and respiratory pathogens in HIV infected patients and the incidence of such infections needs to be carefully assessed.

Natural killer T cells (NKT cells) represent a subset of T lymphocytes that express natural killer (NK) cell surface markers. A subset of NKT cells, termed invariant NKT cells (iNKT), express a highly restricted T cell receptor (TCR) and respond to CD1d-restricted lipid ligands. iNKT cells are now appreciated to play an important role in linking innate and adaptive immune responses and have been implicated in infectious disease, allergy, asthma, autoimmunity, and tumor surveillance. Advances in iNKT identification and purification have allowed for the detailed study of iNKT activity in both humans and mice during a variety of chronic and acute infections. Comparison of iNKT function between non-pathogenic simian immunodeficiency virus (SIV) infection models and chronic HIV-infected patients implies a role for iNKT activity in controlling immune activation. In vitro studies of influenza infection have revealed novel effector functions of iNKT cells including IL-22 production and modulation of myeloid-derived suppressor cells, but ex vivo characterization of human iNKT cells during influenza infection are lacking. Similarly, as recent evidence suggests iNKT involvement in dengue virus pathogenesis, iNKT cells may modulate responses to a number of emerging pathogens. This Review will summarize current knowledge of iNKT involvement in responses to viral infections in both human and mouse models and will identify critical gaps in knowledge and opportunities for future study. We will also highlight recent efforts to harness iNKT ligands as vaccine adjuvants capable of improving vaccination-induced cellular immune responses.

Endophthalmitis is a rare but frequently devastating infection, caused by diverse organisms, including bacteria, viruses, fungi, and parasites. The causative agents of endophthalmitis vary according to the mechanism. The involvement of intraocular structures can result from exogenous spread from ocular trauma, infection of adjacent structures, or as a complication of intraocular surgery. Of the causes of exogenous endophthalmitis, post-operative endophthalmitis is the most frequently encountered; specifically, cataract surgery is the most frequent eye surgery and, thus, leads the list of surgery-associated endophthalmitis. Exogenous source is far more common than endogenous endophthalmitis, a disease that is caused by the hematogenous spread of organisms from a remote infectious site to the eye, leading to severe visual loss. Several large series estimate that endogenous endophthalmitis accounts for 2–15 % of all cases of endophthalmitis. Progressive vitritis is a hallmark for all forms of endophthalmitis, accompanied by intraocular inflammation, loss of vision, pain, and hypopyon. The common presentation consists of reduced vision, conjunctival injection, pain, and eyelid swelling. We reviewed the microbiology of endophthalmitis during a 9-year period in Winnipeg, Canada. Gram-positive bacteria with coagulase-negative staphylococci are the most common causative organisms, reflecting the association with surgical procedures.

Background Natural killer (NK) cells are members of the innate immune system that play an important role in the defense against viral infection. They are also involved in the regulation of adaptive immune responses through cytokine secretion and the interaction with antigen-presenting cells. However, their role in HIV infection is only partially understood. Objective Here we studied the phenotype and function of NK cells of highly HIV-exposed but seronegative (HESN) uninfected commercial sex workers from Kenya who can be epidemiologically defined as relatively resistant to HIV infection. Design The purpose of this study was to gain insight into the role of NK cells in mediating resistance to HIV-1. This information can be used to better understand protection from infection which can be used for informing future design of effective prophylactics and therapeutics for HIV. Methods Whole blood samples were collected from study participants and isolated NK cells and dendritic cells were used in assays for phenotyping and cell function. Results Activated NK cells from resistant women killed autologous immature dendritic cells more efficiently and also secreted more interferon (IFN)-γ than those of uninfected, susceptible women. Interestingly, NK cells from HIV-resistant women were significantly more effective in inducing secretion of IL-12 in immature dendritic cells. Conclusions These data suggest that an altered NK cell-dendritic cell interaction plays an important role in the protection from infection with HIV-1.

Background Cutaneous leishmaniasis (CL) is a vector-borne parasitic disease characterized by the presence of one or more lesions on the skin that usually heal spontaneously after a few months. Most cases of CL worldwide occur in Southwest Asia, Africa and South America, and a number of cases have been reported among troops deployed to Afghanistan. No vaccines are available against this disease, and its treatment relies on chemotherapy. The aim of this study was to characterize parasites isolated from Canadian soldiers at the molecular level and to determine their susceptibility profile against a panel of antileishmanials to identify appropriate therapies. Methodology/Principal Findings Parasites were isolated from skin lesions and characterized as Leishmania tropica based on their pulsed field gel electrophoresis profiles and pteridine reductase 1 (PTR1) sequences. Unusually high allelic polymorphisms were observed at several genetic loci for the L. tropica isolates that were characterized. The drug susceptibility profile of intracellular amastigote parasites was determined using an established macrophage assay. All isolates were sensitive to miltefosine, amphotericin B, sodium stibogluconate (Pentostam) and paromomycin, but were not susceptible to fluconazole. Variable levels of susceptibility were observed for the antimalarial agent atovaquone/proguanil (Malarone). Three Canadian soldiers from this study were successfully treated with miltefosine. Conclusions/Significance This study shows high heterogeneity between the two L. tropica allelic versions of a gene but despite this, L. tropica isolated from Afghanistan are susceptible to several of the antileishmanial drugs available., Author Summary Cutaneous leishmaniasis (CL) is a vector-borne parasitic disease transmitted by the bite of sandflies, resulting in sores on the skin. No vaccines are available, and treatment relies on chemotherapy. CL has been frequently diagnosed in military personnel deployed to Afghanistan and returning from duty. The parasites isolated from Canadian soldiers were characterized by pulsed field gels and by sequencing conserved genes and were identified as Leishmania tropica. In contrast to other Leishmania species, high allelic polymorphisms were observed at several genetic loci for the L. tropica isolates that were characterized. In vitro susceptibility testing in macrophages showed that all isolates, despite their genetic heterogeneity, were sensitive to most antileishmanial drugs (antimonials, miltefosine, amphotericin B, paromomycin) but were insensitive to fluconazole. This study suggests a number of therapeutic regimens for treating cutaneous leishmaniasis caused by L. tropica among patients and soldiers returning from Afghanistan. Canadian soldiers from this study were successfully treated with miltefosine.

Following the 2009 H1N1 pandemic and ongoing sporadic avian-to-human transmission of H5N1 viruses, an emphasis has been placed on better understanding 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). An understanding of the host genetic determinants of susceptibility and severe respiratory illness, however, is currently lacking. By better defining the role of genetic variability in influenza infection and identifying key polymorphisms that impair the host immune response or correlate with protection, we will be able to better identify at-risk populations and new targets for therapeutic interventions and vaccines. This paper will summarize known immunogenetic factors associated with susceptibility or severity of both pH1N1 and H5N1 infections and will also identify genetic pathways and polymorphisms of high relevance for future study.

To the Editor—We read with interest the report by Suleiman et al [1] on the encouraging results of the VICTOR-E1 Phase 2 Trial, demonstrating vicriviroc's good and sustained antiretroviral and immunologic activity over 48 weeks in treatment-experienced HIV-infected individuals. These promising results need to be balanced with caution against the possibility that treatment could lead to more severe manifestations of other viral infections; this is due to the mechanism of action of vicriviroc and the significant role of CCR5 in the response to viral infections other than HIV. CCR5 is a chemokine receptor expressed on a variety of immune cells and is responsible for mediating leukocyte chemotaxis and homing to sites of infection. Until recently, understanding of the role of CCR5 was limited to its role in HIV cell entry and the protection from HIV afforded by its absence. More recent evidence is mounting to link CCR5 receptor deficiency (ie, the presence of the CCR5Δ32 allele) with an increased risk of symptomatic and fatal West Nile virus infection [2–4]. Additionally, a severe adverse reaction to the yellow fever virus vaccine in a CCR5Δ32 heterozygote and an association of the Δ32 mutation with severe tickborne encephalitis symptoms [5, 6] suggest a broader role for CCR5 in flaviviral infections. Several lines of evidence point to the CCR5Δ32 allele being important in determining disease severity of other viral infections, albeit in animal models. In a mouse model, challenge of CCR5-deficient animals with influenza virus was associated with impaired recruitment of CD8+ to the lungs, accompanied by an increased mortality rate [7, 8]. The vicriviroc treatment arms in the Suleiman et al study included 79 participants. Four deaths were reported in the study, including 2 subjects in the placebo group and 2 in the vicriviroc 20 mg treatment group; the latter 2 were attributed to bilateral atypical pneumonia and presumed disseminated tuberculosis, complicated by multiple organ failure. The concept of targeting a human receptor has numerous advantages but is also accompanied by concerns for untoward effects, especially when the receptor blocked is nonspecific for a given pathogen and has an important role in the general function of cellular immunity against other viruses. In the future, the encouraging results of this trial should be followed up by studying additional patients with specific attention to other viral infections and for a longer follow-up period.

Because chemokine receptor 5 (CCR5) may have a role in pulmonary immune response, we explored whether patients with severe pandemic (H1N1) 2009 were more likely to carry the CCR5Δ32 allele than were members of the general population. We found a large proportion of heterozygosity for the CCR5Δ32 allele among white patients with severe disease.

Background: Hospitalization and lab confirmed cases of H1N1 have been reported during the first wave of the 2009 pandemic but these are not accurate measures of influenza incidence in the population. We estimated the cumulative incidence of pandemic (H1N1) influenza among pregnant women in the province of Manitoba during the first wave of the 2009 pandemic. Methods: Two panels of stored frozen serum specimens collected for routine prenatal screening were randomly selected for testing before (March 2009, n = 252) and after (August 2009, n = 296) the first wave of the pandemic. A standard hemagglutination inhibition assay was used to detect the presence of IgG antibodies against the pandemic (H1N1) 2009 virus. The cumulative incidence of pandemic (H1N1) influenza was calculated as the difference between the point prevalence rates in the first and second panels. Results: Of the specimens collected in March, 7.1% were positive for the IgG antibodies (serum antibody titre ≥ 1:40). The corresponding prevalence was 15.7% among the specimens collected in August. The difference indicated a cumulative incidence of 8.6% (95% confidence interval [CI] 3.2%–13.7%). The rate differed geographically, the highest being in the northern regions (20.8%, 95% CI 7.9%–31.8%), as compared with 4.0% (95% CI 0.0%–11.9%) in Winnipeg and 8.9% (95% CI 0.0%–18.8%) in the rest of the province. Interpretation: We estimated that the cumulative incidence of pandemic (H1N1) influenza among pregnant women in Manitoba during the first wave of the 2009 pandemic was 8.6%. It was 20.8% in the northern regions of the province.

Community-acquired pyogenic liver abscess caused by Klebsiella pneumoniae is an emerging infectious disease. We explored the capsular polysaccharide synthesis ( cps ) regions of three non-K1, non-K2 K. pneumoniae strains, A1142, A7754, and A1517, from Taiwanese patients experiencing pyogenic liver abscess. Two of the strains, A1142 and A7754, belonged to capsular serotype K57, while the third belonged to a new capsular serotype, different from the previously reported 77 serotypes. Deletion and complementation experiments suggested that a unique K57 gene, a homologue of wzy , was essential for K57 capsular synthesis and confirmed that this gene cluster was a genetic coding region for K57. Compared to K1 and K2 strains, the three strains were all serum sensitive, suggesting that host factors might also be involved in the three patients. PCR using primers from specific genes for K57 was more sensitive and specific than traditional serotyping. The remaining strain, A1517, did not react to the antisera from any of the 77 serotypes, and none of the 77 reference strains reacted to the serum against this strain. Moreover, PCR analyses using various primer pairs from the serotype-specific open reading frames did not reveal cross-reactivity to any of the 77 reference strains, suggesting that this strain likely represents a new capsular type. We conclude that sequences from these two cps regions are very useful in detecting K57 and the new cps genotype.

We present a case of Acremonium vertebral osteomyelitis that relapsed despite surgical debridement and prolonged treatment with liposomal amphotericin B, but which responded to voriconazole therapy. The report highlights the role of molecular diagnosis of rare fungal osteomyelitis. The patient was successfully treated with voriconazole.

This report describes a case of granulomatous inflammation, involving the bone marrow and skin, due toBartonellainfection in an immunocompetent patient. The clinical presentation included prolonged fever, pancytopenia, rash and hepatitis.Bartonellainfection should thus be added to the growing list of entities that produce marrow granulomas and fever.

HLA-C was shown to be a highly polymorphic gene that can be accurately typed by sequencing methodologies. We report two novel HLA-C alleles identified during sequence-based typing of East African populations; the novel alleles were confirmed by sequencing two separate polymerase chain reaction products and by molecular cloning and sequencing multiple clones. The first new allele is identical to Cw*0701 except for a single-nucleotide synonymous substitution at codon 182 (GCA--GCG). The new allele has been named by the WHO nomenclature committee as Cw*070105. The second new allele is identical to Cw*1403 except for a nonsynonomous change at codon 21 (CAC--CGC), changed from histidine to arginine. The new allele has been named by the WHO nomenclature committee as Cw*1408.

Blood culture negative endocarditis is defined as definite or probable endocarditis in which three or more aerobic and anaerobic blood cultures collected over 48 h remain negative despite prolonged (greater than 1 week) incubation. Culture negative endocarditis constitutes a significant percentage of all cases of endocarditis in an institution and is a particularly challenging condition for the clinician treating such a patient. An organized approach to diagnosis and treatment is necessary. The most common cause of culture negative endocarditis is prior antibiotic therapy but an increasing number of organisms that cannot be grown in blood cultures given current techniques account for a varying percentage of cases depending on geographic location and laboratory technology. Nucleic acid amplification techniques, immunohistochemistry and transmission electron microscopy on vegetations all have a role in making a diagnosis. In hospital mortality is similar to that of culture positive endocarditis.

Carbon monoxide, a byproduct of incomplete hydrocarbon combustion, has been responsible for many accidental poisonings worldwide. The signs and symptoms of poisoning are diverse, ranging from headache, dizziness, and confusion to cardiac and neurological disturbances. Oxygen is the cornerstone of treatment, because it accelerates the dissociation of carbon monoxide from heme proteins. The role of hyperbaric oxygen in the treatment of CO poisoning is still questionable. Only a few randomized, controlled studies have been conducted, and their results are inconsistent. In the present review, we discuss the conclusions of four randomized controlled studies and propose a hyperbaric oxygen treatment protocol based on these conclusions.

Acute pulmonary edema has been noted in swimmers and divers, and has been termed swimming-induced pulmonary edema (SIPE). The mechanisms and consequences of SIPE are unknown, and there are currently no series of carefully evaluated patients with this condition. Herein we report the clinical presentation, incidence of recurrence, findings on physical examination, chest radiography, and oxygen saturation in 70 trainees with a diagnosis of SIPE. We also report the results of forced spirometry in a subgroup of 37 swimmers.SIPE was diagnosed when severe shortness of breath and cough were reported during or after swimming, and were associated with evidence of pulmonary edema. During the years from 1998 to 2001, 70 cases of SIPE were documented in young healthy male subjects participating in a fitness-training program. Physical examination and pulse oximetry were performed immediately. Chest radiographs were obtained in all cases 12 to 18 h following onset of symptoms. In 37 swimmers, spirometry was performed at the time of chest radiography and again after 7 days.All subjects complained of severe shortness of breath. Sixty-seven of the 70 subjects (95.7%) had a prominent cough; in 63 subjects (90%), there was significant sputum production. Hemoptysis was observed in 39 subjects (55.7%). Mean arterial oxygen saturation after swimming was 88.4 +/- 6.6% breathing air, compared with 98 +/- 1.7% breathing air at rest before the start of the swimming trial (mean +/- SD) [p0.001]. Chest radiographs obtained 12 to 18 h after swimming were normal in all cases. Sixteen trainees (22.9%) had a recurrence of SIPE. Spirometry demonstrated restrictive lung function, which persisted for a week.In our trainee population, SIPE is a not uncommon, often recurrent phenomenon that significantly influences performance. It is not clear what predisposes to its occurrence or recurrence and what, if any, are its long-term effects.

Acute pulmonary edema may be induced by diving and strenuous swimming. We report the case of a diver using closed-circuit, scuba equipment who developed acute dyspnea, hemoptysis, and hypoxemia following a dive in 18 degreesC (64.4 degrees F) water and physical exertion during the swim back to shore. With the growing popularity of recreational scuba diving, emergency physicians are liable to be faced with increasing numbers of diving-related medical problems. Diving-induced pulmonary edema should be included in the differential diagnosis of acute hypoxemia, sometimes accompanied by acid-base abnormalities, when this is seen in a diver.

The diagnosis of venous thromboembolism (VTE) (deep vein thrombosis and pulmonary embolism) poses a challenge for physicians in emergency departments (EDs). Clinical findings and non-specific laboratory tests are usually insufficient to rule out VTE. Due to high costs, higher complication rates, and other reasons, the "gold standard" tests for VTE (pulmonary angiography or contrast venography) are usually unavailable and are seldom used by most physicians in the EDs. The end result is an extensive use of the non-invasive Imaging modalities and yet under-diagnosis of VTE. The purpose of this review is to describe the advanced non-invasive methods currently available for the diagnosis of VTE and to define the role of the rapid d-dimer assay. We also propose a practical diagnostic protocol for VTE that is based on a combination of D-dimer test and judicious use of non-invasive imaging, which may be implemented in all emergency departments.

Canadian data regarding the characteristics of HIV-positive patients admitted to hospital as well as the causes and patterns of admissions remain limited. Chart reviews were performed to ascertain admission diagnosis, co-morbidities and CD4 counts among this sub-population, which had an over-representation of Aboriginal persons. Infectious diseases, particularly pneumonia, represent the most common admission diagnosis for HIV-positive persons in Winnipeg. Further, individuals presenting to hospital often have very low CD4 counts, representing significant immune suppression. Earlier HIV diagnosis and treatment in an effort to delay the onset of advanced disease and hospitalization is needed.

A case of catheter-related bacteraemia caused by Exiguobacterium acetylicum is reported in an elderly patient. The availability of sequence-based methods facilitated rapid identification and expanded the spectrum of diseases attributed to coryneform bacteria and specifically to the genus Exiguobacterium.

Background Influenza infection may be more serious in human immunodeficiency virus (HIV)-infected individuals, therefore, vaccination against seasonal and pandemic strains is highly advised. Seasonal influenza vaccines have had no significant negative effects in well controlled HIV infection, but the impact of adjuvanted pandemic A/California/07/2009 H1N1 influenza hemaglutinin (HA) vaccine, which was used for the first time in the Canadian population as an authorized vaccine in autumn 2009, has not been extensively studied. Objective Assess vaccine-related effects on CD4+ T cell counts and humoral responses to the vaccine in individuals attending the Newfoundland and Labrador Provincial HIV clinic. Methods A single dose of ArepanrixTM split vaccine including 3.75 μg A/California/07/2009 H1N1 HA antigen and ASO3 adjuvant was administered to 81 HIV-infected individuals by intramuscular injection. Plasma samples from shortly before, and 1–5 months after vaccination were collected from 80/81 individuals to assess humoral anti-H1N1 HA responses using a sensitive microbead-based array assay. Data on CD4+ T cell counts, plasma viral load, antiretroviral therapy and patient age were collected from clinical records of 81 individuals. Results Overall, 36/80 responded to vaccination either by seroconversion to H1N1 HA or with a clear increase in anti-H1N1 HA antibody levels. Approximately 1/3 (28/80) had pre-existing anti-H1N1 HA antibodies and were more likely to respond to vaccination (22/28). Responders had higher baseline CD4+ T cell counts and responders without pre-existing antibodies against H1N1 HA were younger than either non-responders or responders with pre-existing antibodies. Compared to changes in their CD4+ T cell counts observed over a similar time period one year later, vaccine recipients displayed a minor, transient fall in CD4+ T cell numbers, which was greater amongst responders. Conclusions We observed low response rates to the 2009 pandemic influenza vaccine among HIV-infected individuals without pre-existing antibodies against H1N1 HA and a minor transient fall in CD4+ T cell numbers, which was accentuated in responders. A single injection of the ArepanrixTM pandemic A/California/07/2009 H1N1 HA split vaccine may be insufficient to induce protective immunity in HIV-infected individuals without pre-existing anti-H1N1 HA responses.