Thomas J. Marrie

HMDB: the Human Metabolome Database

The Human Metabolome Database (HMDB) is currently the most complete and comprehensive curated collection of human metabolite and human metabolism data in the world. It contains records for more than 2180 endogenous metabolites with information gathered from thousands of books, journal articles and electronic databases. In addition to its comprehensive literature-derived data, the HMDB also contains an extensive collection of experimental metabolite concentration data compiled from hundreds of mass spectra (MS) and Nuclear Magnetic resonance (NMR) metabolomic analyses performed on urine, blood and cerebrospinal fluid samples. This is further supplemented with thousands of NMR and MS spectra collected on purified, reference metabolites. Each metabolite entry in the HMDB contains an average of 90 separate data fields including a comprehensive compound description, names and synonyms, structural information, physico-chemical data, reference NMR and MS spectra, biofluid concentrations, disease associations, pathway information, enzyme data, gene sequence data, SNP and mutation data as well as extensive links to images, references and other public databases. Extensive searching, relational querying and data browsing tools are also provided. The HMDB is designed to address the broad needs of biochemists, clinical chemists, physicians, medical geneticists, nutritionists and members of the metabolomics community. The HMDB is available at:

Canadian Guidelines for the Initial Management of Community-Acquired Pneumonia: An Evidence-Based Update by the Canadian Infectious Diseases Society and the Canadian Thoracic Society

Lionel A Mandell MD FRCPC1, Thomas J Marrie MD FRCPC2, Ronald F Grossman MD FRCPC FACP3, Anthony W Chow MD FRCPC FACP4, Robert H Hyland MD FRCPC5, and the Canadian CAP Working Group* McMaster University, Hamilton, Ontario; Dalhousie University, Halifax, Nova Scotia; QEII Health Sciences Centre, Halifax, Nova Scotia; University of British Columbia, Vancouver, British Columbia; St Michael’s Hospital, Toronto, Ontario

Natural history and pathophysiology of Q fever

Q fever is a zoonosis caused by Coxiella burnetii. Infection with C burnetii can be acute or chronic, and exhibits a wide spectrum of clinical manifestations. The extreme infectivity of the bacterium results in large outbreaks and makes it a potential bioweapon. In the past decade, the complete genome sequencing of C burnetii, the exploration of bacterial interactions with the host, and the description of the natural history of the disease in human beings and in experimental models have all added to our knowledge about this fascinating disease. Advances in understanding the pathophysiology and natural history of Q fever are reviewed.

Cultivation of the bacillus of Whipple's disease

BACKGROUND Whipples disease is a systemic bacterial infection, but to date no isolate of the bacterium has been established in subculture, and no strain of this bacterium has been available for study. METHODS Using specimens from the aortic [corrected] valve of a patient with endocarditis due to Whipples disease, we isolated and propagated a bacterium by inoculation in a human fibroblast cell line (HEL) with the use of a shell-vial assay. We tested serum samples from our patient, other patients with Whipples disease, and control subjects for the presence of antibodies to this bacterium. RESULTS The bacterium of Whipples disease was grown successfully in HEL cells, and we established subcultures of the isolate. Indirect immunofluorescence assays showed that the patients serum reacted specifically against the bacterium. Seven of 9 serum samples from patients with Whipples disease had IgM antibody titers of 1:50 or more, as compared with 3 of 40 samples from the control subjects (P<0.001). Polyclonal antibodies against the bacterium were generated by inoculation of the microorganism into mice and were used to detect bacteria in the excised cardiac tissue from our patient on immunohistochemical analysis. The 16S ribosomal RNA gene of the cultured bacterium was identical to the sequence for Tropheryma whippelii identified previously in tissue samples from patients with Whipples disease. The strain we have grown is available in the French National Collection. CONCLUSIONS We cultivated the bacterium of Whipples disease, detected specific antibodies in tissue from the source patient, and generated specific antibodies in mice to be used in the immunodetection of the microorganism in tissues. The development of a serologic test for Whipples disease may now be possible.

Community-Acquired Pneumonia in the Elderly

Pneumonia in the elderly is a common and serious problem with a clinical presentation that can differ from that in younger patients. Older patients with pneumonia complain of significantly fewer symptoms than do younger patients, and delirium commonly occurs. Indeed, delirium may be the only manifestation of pneumonia in this group of patients. Alcoholism, asthma, immunosuppression, and age >70 years are risk factors for community-acquired pneumonia in the elderly. Among nursing home residents, the following are risk factors for pneumonia: advanced age, male sex, difficulty in swallowing, inability to take oral medications, profound disability, bedridden state, and urinary incontinence. Streptococcus pneumoniae is the most common cause of pneumonia among the elderly. Aspiration pneumonia is underdiagnosed in this group of patients, and tuberculosis always should be considered. In this population an etiologic diagnosis is rarely available when antimicrobial therapy must be instituted. Use of the guidelines for treatment of pneumonia issued by the Infectious Diseases Society of America, with modification for treatment in the nursing home setting, is recommended.

Burden of community-acquired pneumonia in North American adults.

Abstract To determine the burden of community-acquired pneumonia (CAP) affecting adults in North America, a comprehensive literature review was conducted to examine the incidence, morbidity and mortality, etiology, antibiotic resistance, and economic impact of CAP in this population. In the United States, there were approximately 4.2 million ambulatory care visits for pneumonia in 2006. Pneumonia and influenza continue to be a common cause of death in the United States (ranked eighth) and Canada (ranked seventh). In 2005, there were > 60 000 deaths due to pneumonia in persons aged ≥ 15 years in the United States alone. The hospitalization rate for all infectious diseases increased from 1525 hospitalizations per 100 000 persons in 1998 to 1667 per 100 000 persons in 2005. Admission to an intensive care unit was required in 10% to 20% of patients hospitalized with pneumonia. The mean length of stay for pneumonia was ≥ 5 days and the 30-day rehospitalization rate was as high as 20%. Mortality was highest for CAP patients who were hospitalized; the 30-day mortality rate was as high as 23%. All-cause mortality for CAP patients was as high as 28% within 1 year. Streptococcus pneumoniae continues to be the most frequently identified pathogen associated with CAP, and pneumococcal resistance to antimicrobials may make treatment more difficult. The economic burden associated with CAP remains substantial at >

RICKETTSIA AFRICAE, A TICK-BORNE PATHOGEN IN TRAVELERS TO SUB-SAHARAN AFRICA

17 billion annually in the United States. Despite the availability and widespread adherence to recommended treatment guidelines, CAP continues to present a significant burden in adults. Furthermore, given the aging population in North America, clinicians can expect to encounter an increasing number of adult patients with CAP. Given the significance of the disease burden, the potential benefit of pneumococcal vaccination in adults is substantial.

Statins and outcomes in patients admitted to hospital with community acquired pneumonia : population based prospective cohort study

BACKGROUND African tick-bite fever occurs after contact with ticks that carry Rickettsia africae and that parasitize cattle and game. Sporadic reports suggest that this infection has specific clinical and epidemiologic features. METHODS We studied patients who were tested for a rickettsial disease after returning from a visit to Africa or Guadeloupe. To assess the value of the microimmunofluorescence assay, Western blotting, and cross-adsorption assays, we compared the results of these tests in 39 patients in whom African tick-bite fever had been confirmed by the polymerase-chain reaction assay, cell culture, or both; 50 patients with documented R. conorii infection; and 50 blood donors. These diagnostic criteria were then applied to 376 additional patients who had returned from southern Africa and 2 who had returned from Guadeloupe and whose serum was being tested for rickettsial disease. RESULTS In the 39 patients with direct evidence of R. africae infection, the combination of microimmunofluorescence assay, Western blotting, and cross-adsorption assays showing antibodies specific for R. africae had a sensitivity of 0.56; however, each test had a positive predictive value and a specificity of 1.0. An additional 80 patients were found to have an R. africae infection on the basis of these serologic criteria. Infections with R. africae were acquired by visitors to 11 African countries and Guadeloupe. The illness was generally mild and was characterized by a rash in 46 percent of the patients; the rash was usually maculopapular or vesicular and rarely purpuric. Ninety-five percent of patients had an inoculation eschar or eschars, and 54 percent of these patients had multiple eschars, a finding that is unusual in patients with rickettsial infection. CONCLUSIONS In this series, R. africae was the cause of nearly all cases of tick-bite rickettsiosis in patients who became ill after a trip to sub-Saharan Africa.

Viral Infection in Adults Hospitalized With Community-Acquired Pneumonia: Prevalence, Pathogens, and Presentation

Objectives To determine whether statins reduce mortality or need for admission to intensive care in patients admitted to hospital with community acquired pneumonia; and to assess whether previously reported improvements in sepsis related outcomes were a result of the healthy user effect. Design Population based prospective cohort study. Setting Six hospitals in Capital Health, Edmonton, Alberta, Canada. Participants Adults admitted to hospital with pneumonia and categorised according to use of statins for at least one week before admission and during hospital stay. Main outcome measures Composite of in-hospital mortality or admission to an intensive care unit. Results Of 3415 patients with pneumonia admitted to hospital, 624 (18%) died or were admitted to an intensive care unit. Statin users were less likely to die or be admitted to an intensive care unit than non-users (50/325 (15%) v 574/3090 (19%), odds ratio 0.80, P=0.15). After more complete adjustment for confounding, however, the odds ratios changed from potential benefit (0.78, adjusted for age and sex) to potential harm (1.10, fully adjusted including propensity scores, 95% confidence interval 0.76 to1.60). Conclusions Statins are not associated with reduced mortality or need for admission to an intensive care unit in patients with pneumonia; reports of benefit in the setting of sepsis may be a result of confounding.

A Randomized Controlled Trial of Filgrastim as an Adjunct to Antibiotics for Treatment of Hospitalized Patients with Community-Acquired Pneumonia

Background The potential role of respiratory viruses in the natural history of community-acquired pneumonia (CAP) in adults has not been well described since the advent of nucleic amplification tests (NATs). Methods From 2004 to 2006, adults with CAP who were admitted to five hospitals were prospectively enrolled in the study, and clinical data, cultures, serology, and nasopharyngeal swabs were obtained. NATs from swabs were tested for influenza, human metapneumovirus (hMPV), respiratory syncytial virus (RSV), rhinovirus, parainfluenza virus 1–4, coronaviruses (OC43, 229E, and NL63), and adenovirus. Results A total of 193 patients were included; the median age was 71 years, 51% of patients were male, and 47% of patients had severe CAP. Overall, 75 patients (39%) had a pathogen identified. Of these pathogens, 29 were viruses (15%), 38 were bacteria (20%), 8 were mixed (4%), and the rest were “unknown.” Influenza (n = 7), hMPV (n = 7), and RSV (n = 5) accounted for most viral infections; other infections included rhinovirus (n = 4), parainfluenza (n = 3), coronavirus (n = 4), and adenovirus (n = 2). Streptococcus pneumoniae was the most common bacterial infection (37%). Compared with bacterial infection, patients with viral infection were older (76 vs 64 years, respectively; p = 0.01), were more likely to have cardiac disease (66% vs 32%, respectively; p = 0.006), and were more frail (eg, 48% with limited ambulation vs 21% of bacterial infections; p = 0.02). There were few clinically meaningful differences in presentation and no differences in outcomes according to the presence or absence of viral infection. Conclusions Viral infections are common in adults with pneumonia. Easily transmissible viruses such as influenza, hMPV, and RSV were the most common, raising concerns about infection control. Routine testing for respiratory viruses may be warranted for adults who have been hospitalized with pneumonia.