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The optimal treatment for potential AmpC-producing Enterobacteriaceae, including Serratia, Providencia, Citrobacter, Enterobacter, and Morganella species, remains unknown. An updated systematic review and meta-analysis of studies comparing beta-lactam/beta-lactamase inhibitors with carbapenems in the treatment of bloodstream infections with these pathogens found no significant difference in 30-day mortality (OR, 1.13; 95% CI, 0.58 – 2.20)., The optimal treatment of bloodstream infections caused by potential AmpC-producing organisms is unsettled. A systematic review with meta-analysis found no significant difference in 30-day mortality in patients who were treated with beta-lactam/beta-lactamase inhibitors compared with carbapenems.

Background Global action plans to tackle antimicrobial resistance (AMR) include implementation of antimicrobial stewardship (AMS), but few studies have directly addressed the challenges faced by low and middle-income countries (LMICs). Our aim was to explore healthcare providers’ knowledge and perceptions on AMR, and barriers/facilitators to successful implementation of a pharmacist-led AMS intervention in a referral hospital in Ethiopia. Methods Tikur Anbessa Specialized Hospital (TASH) is an 800-bed tertiary center in Addis Ababa, and the site of an ongoing 4-year study on AMR. Between May and July 2017, using a mixed approach of quantitative and qualitative methods, we performed a cross-sectional survey of pharmacists and physicians using a pre-tested questionnaire and semi-structured interviews of purposively selected respondents until thematic saturation. We analyzed differences in proportions of agreement between physicians and pharmacists using χ2 and fisher exact tests. Qualitative data was analyzed thematically. Findings A total of 406 survey respondents (358 physicians, 48 pharmacists), and 35 key informants (21 physicians and 14 pharmacists) were enrolled. The majority of survey respondents (>90%) strongly agreed with statements regarding the global scope of AMR, the need for stewardship, surveillance and education, but their perceptions on factors contributing to AMR and their knowledge of institutional resistance profiles for common bacteria were less uniform. Close to 60% stated that a significant proportion of S. aureus infections were caused by methicillin-resistant strains (an incorrect statement), while only 48% thought a large proportion of gram-negative infections were caused by cephalosporin-resistant strains (a true statement). Differences were noted between physicians and pharmacists: more pharmacists agreed with statements on links between use of broad-spectrum antibiotics and AMR (p

Human enteric parasitoses, particularly from Cryptosporidium, were recently recognized as being highly prevalent in parts of the Arctic. This is important because cryptosporidiosis has been repeatedly associated with impaired growth and development and may synergize with other challenges faced by children in remote Arctic communities, such as overcrowding and food insecurity.

Ten Belgian travelers returned from Mali with a Schistosoma haematobium-Schistosoma bovis hybrid infection, confirmed by DNA sequencing from eggs. Clinical symptoms and laboratory findings resembled those of classic acute schistosomiasis, but the detected eggs were morphologically unusual.

In late summer, a previously healthy 52-year-old woman was swimming in a lake in southern Quebec when she was bitten by a marine animal. As she swam toward shore, she and a nearby friend recognized it as a river otter ( Lontra canadensis; see [Figure 1][1]), which began to aggressively pursue her

BACKGROUND Due to ongoing political instability and conflict in many parts of the world, migrants are increasingly seeking asylum and refuge in Canada. METHODS We examined demographic and travel correlates of illnesses among migrants to Canada to establish a detailed epidemiologic framework of this population for Canadian practitioners. Data on ill-returned Canadian travellers presenting to a CanTravNet site between 1 January 2015 and 31 December 2015 were analyzed. RESULTS During the study period, 2415 ill travellers and migrants presented to a CanTravNet site, and of those, 519 (21.5%) travelled for the purpose of migration. Sub-Saharan Africa (n = 160, 30.8%), southeast Asia (n = 84, 16.2%) and south central Asia (n = 75, 14.5%) were the most common source regions for migrants, while the top specific source countries, of 98 represented, were the Philippines (n = 45, 8.7%), China (n = 36, 6.9%) and Vietnam (n = 31, 6.0%). Compared with non-migrant travellers, migrants were more likely to have a pre-existing immunocompromising medical condition, such as HIV or diabetes mellitus (P < 0.0001), and to require inpatient management of their illness (P < 0.0001). Diagnoses such as tuberculosis (n = 263, 50.7%), hepatitis B and C (n = 78, 15%) and HIV (n = 11, 2.1%) were over-represented in the migrant population compared with non-migrant travellers (P < 0.0001). Most cases of tuberculosis in the migrant population (n = 263) were latent (82% [n = 216]); only 18% (n = 47) were active. CONCLUSIONS Compared with non-migrant travellers, migrants were more likely to present with a communicable infectious disease, such as tuberculosis, potentially complicated by an underlying immunosuppressing condition such as HIV. These differences highlight the divergent healthcare needs in the migrant population, and underscore the importance of surveillance programmes to understand their burden of illness. Intake programming should be adequately resourced to accommodate the medical needs of this vulnerable population of new Canadians.

Background Current guidelines recommend obtaining blood cultures prior to antimicrobial therapy in patients with sepsis. Administering antimicrobials immediately without waiting for blood cultures could potentially decrease time to treatment and improve outcomes, but it is unclear the degree to which this strategy impacts diagnostic yield. Methods We performed a patient-level, single-arm, diagnostic trial. Seven urban emergency departments affiliated with academic medical centers across Canada and the United States participated in the study. Adults ≥18 years of age presenting to the emergency department with evidence of severe manifestations of sepsis, including a systolic blood pressure Results Of the 3,164 participants screened, 325 were included in the study (mean age, 65.6 years; 63.0% men) and had repeat blood cultures drawn after the initiation of antimicrobial therapy (median time of 70 minutes, IQR 50 to 110 minutes). Pre-antimicrobial blood cultures were positive for one or more microbial pathogens in 102/325 (31.4%) patients. Fifty-four participants (52.9%) had matching blood culture results after initiation of antimicrobial treatment. The absolute difference in pathogen recovery rates was 14.5% ([95% CI 8.0 to 21.0%]; P < 0.0001) between pre- and post-antimicrobial blood cultures. Results were consistent in an analysis of the per-protocol population (absolute difference, 13.3% [95% CI 6.1 to 20.4%]; P < 0.0001). Including the results of other microbiological cultures done as part of routine care, microbial pathogens were recovered in 69 of 102 (67.7%) participants (absolute difference, 10.2% [95% CI 3.4 to 16.8%]; P < 0.0001). Conclusion Among patients with severe manifestations of sepsis, the administration of empiric antimicrobial therapy significantly reduces the yield of pathogen recovery when blood cultures are drawn shortly after treatment initiation. Disclosures All Authors: No reported Disclosures.

Bacteremia due to Cloacibacillus species is poorly described. We present three cases involving either Cloacibacillus evryensis or Cloacibacillus porcorum . The isolates were identified by 16S rRNA gene sequencing and were susceptible to antibiotics commonly used for anaerobic infections. The clinical significance of these organisms as potential emerging pathogens is discussed.

Infectious diseases acquired during travel pose a significant health risk to pregnant travellers, who are more susceptible to both acquiring certain infections and developing severe complications. A review of the literature focusing on recent evidence-based guidelines was conducted with attention to tropical infections in the pregnant patient. A summary meant to serve as a succinct reference for health care professionals caring for pregnant women is presented. Magnitude of risk, clinical features, management, and preventive strategies of major travel-acquired infections of pertinence to the pregnant traveller are summarized, including malaria, arboviral infections, foodborne infections, helminthic infections, and influenza. Tables with details on specific infections within each group and guidance for reducing travel-related health risks in the pregnant patient are presented.

We thank Dr. Jansz[1][1] for his interest in our surveillance report.[2][2] We recognize that understanding the intricacies of the CanTravNet data would be difficult without first-hand experience of our network and its patient population. CanTravNet is a consortium of post-travel (not pretravel)

Background Cancer is a known risk factor for developing active tuberculosis (TB). We determined the incidence and relative risk of active TB in cancer patients compared to the general population. Methods Electronic databases were searched up to December 2015: Medline, Medline InProcess, EMBASE, PubMed, the Cochrane Database of Systematic Reviews, Cancerlit, and Web of Science. Studies of pathologically confirmed cancer patients were included if active TB was identified concurrently or after the diagnosis. Cumulative incidence rate/100,000 population (CIR) of new cases of TB occurring in cancer patients and comparative incidence rate ratios (IRR) to the general population from the same country of origin were estimated. A random effect meta-analysis was conducted on the CIR and IRR. Results A total of 23 studies reporting 593 TB cases occurring in 324,041 cancer patients between 1950 and 2011 were identified. In a meta-analysis of 6 studies conducted in the US in 317,243 cancer patients (98% of all patients) the CIR of active TB decreased by 3 fold and 6.5 fold in hematologic and solid cancers respectively before and after 1980. After 1980 the CIR of active TB was highest in hematologic (219/100,000 population, IRR=26), head and neck (143; 16), lung cancers (83; 9) and was lowest in breast and other solid cancers (38; 4). Conclusions Individuals living in the US with hematologic, head and neck, and lung cancers had a 9-fold higher rate of developing active TB compared to those without cancer and would benefit from targeted latent TB screening and therapy.

Background There are increasing data regarding Terrisporobacter glycolicus as an emerging anaerobic pathogen. However, the few published cases to date usually report it as part of a polymicrobial infection. Here, we describe the first reported monomicrobial surgical site infection with this bacterium. Identification methods, taxonomy, and clinical management of this rarely identified pathogen are also discussed. Case presentation A previously healthy 66-year-old sustained an open olecranon fracture of his left arm after trauma. He subsequently underwent open reduction and internal fixation (ORIF), with insertion of an olecranon locking plate and two locking screws. Ten days after surgery, the patient developed increasing pain at the surgical site and noted green discharge from the wound. Culture of the wound discharge yielded grew a pure Gram-positive anaerobe identified by the RapidANA® microbial identification system as C. difficile (profile 000010, 99.1 % probability). Reference laboratory testing identified the isolate as T. glycolicus/mayombei (previously designated as Clostridium glycolicum/mayombei) by 16S rRNA gene sequencing and as Clostridium glycolicum by MALDI-TOF mass spectrometry. The patient received an 8-week course of moxifloxacin and metronidazole with an excellent clinical response at 12 months’ follow-up. Conclusions We describe the case of a deep surgical site infection with T. glycolicus/mayombei (formerly known as Clostridium glycolicum and Clostridium mayombei, respectively), which extends our knowledge of the clinical spectrum of this pathogen. The isolate was misidentified by phenotypic identification methods.

Visceral leishmaniasis (VL) is a fatal parasitic disease. Unfortunately, diagnosis of VL in east Africa currently relies on aspiration of tissue from the spleen or bone marrow, which is painful and potentially dangerous. We sought to determine whether peripheral blood could be used instead of invasive tissue aspirates to diagnose VL, using three parasite concentration techniques. Three hundred and one consecutive people suspected of having VL were recruited. Compared with microscopy of tissue aspirates, the diagnostic accuracy of peripheral blood microscopy was as follows: whole blood thin smear sensitivity 1.5% (95% confidence interval [CI] 0.0-8.3) and specificity 100% (95% CI 76.8-100); buffy-coat smear sensitivity 19.5% (95% CI 14.3-25.6) and specificity 98.9% (95% CI 94.1-100); peripheral blood mononuclear cell (PBMC) smear sensitivity 33.7% (95% CI 27.3-40.5) and specificity 95.7% (95% CI 89.6-98.6). Sensitivity of PBMC smears was significantly higher in human immunodeficiency virus (HIV)-coinfected patients (N = 48/301); two-sample test of proportions, P = 0.0097; sensitivity 55.9% (95% CI 37.9-72.8) and specificity 92.9% (95% CI 66.1-99.8), and correlated with the degree of parasite load in the tissue. Combining the results from smears of both PBMC and buffy coat yielded a sensitivity and specificity of 67.6% (95% CI 49.1-82.6) and 92.9% (95% CI 66.1-99.8), respectively, in HIV-coinfected patients. In this setting, VL could be ruled-in with peripheral blood microscopy in a substantial number of VL suspects and may reduce the number of tissue aspirations performed, particularly in HIV-coinfected patients. More sensitive and logistically feasible methods than light microscopy are needed to detect Leishmania donovani parasites present in blood.

Background Cryptosporidium is a leading cause of childhood diarrhea in low-resource settings, and has been repeatedly associated with impaired physical and cognitive development. In May 2013, an outbreak of diarrhea caused by Cryptosporidium hominis was identified in the Arctic region of Nunavik, Quebec. Human cryptosporidiosis transmission was previously unknown in this region, and very few previous studies have reported it elsewhere in the Arctic. We report clinical, molecular, and epidemiologic details of a multi-village Cryptosporidium outbreak in the Canadian Arctic. Methodology/Principal Findings We investigated the occurrence of cryptosporidiosis using a descriptive study of cases with onset between April 2013 and April 2014. Cases were defined as Nunavik inhabitants of any age presenting with diarrhea of any duration, in whom Cryptosporidium oocysts were detected by stool microscopy in a specialised reference laboratory. Cryptosporidium was identified in stool from 51 of 283 individuals. The overall annual incidence rate (IR) was 420 / 100,000 inhabitants. The IR was highest among children aged less than 5 years (1290 /100,000 persons). Genetic subtyping for stool specimens from 14/51 cases was determined by DNA sequence analysis of the 60 kDa glycoprotein (gp60) gene. Sequences aligned with C. hominis subtype Id in all cases. No common food or water source of infection was identified. Conclusions/Significance In this first observed outbreak of human cryptosporidiosis in this Arctic region, the high IR seen is cause for concern about the possible long-term effects on growth and development of children in Inuit communities, who face myriad other challenges such as overcrowding and food-insecurity. The temporal and geographic distribution of cases, as well as the identification of C. hominis subtype Id, suggest anthroponotic rather than zoonotic transmission. Barriers to timely diagnosis delayed the recognition of human cryptosporidiosis in this remote setting., Author Summary In mid-2013, an outbreak of moderate-to-severe diarrhea caused by Cryptosporidium was identified in the Arctic region of Nunavik, Quebec, and it predominantly affected young children. Cryptosporidium is a leading cause of childhood diarrhea in low-resource settings, but was previously unknown in this region. This is important because cryptosporidiosis has been repeatedly associated with impaired growth and development, and may interact with other challenges currently faced by children in remote Arctic communities, such as overcrowding and food-insecurity. Although animals in the Arctic have previously been found to harbour Cryptosporidium parvum, which can infect both animals and humans, we found that the Cryptosporidium identified in the stool of affected people all belonged to the species C. hominis, which is only known to infect humans. Together with the temporal and geographic distribution of cases, this suggests that cryptosporidiosis in this outbreak was transmitted person-to-person, rather than acquired from contact with animals. The emergence of Cryptosporidium infections in Arctic communities may have public health impacts beyond the occurrence of diarrhea.

Background Certain organisms, including Serratia, Providentia, Acinetobacter, Citrobacter, Enterobacter, and Morganella species (SPACE-M) may possess an inducible broad-spectrum β-lactamase, AmpC, which is not inhibited by most β-lactamase inhibitors. Our objective was to determine whether treating SPACE-M bloodstream infections (BSI) with potentially hydrolyzable β-lactams was associated with increased risk of 30-day mortality. Methods A retrospective cohort study was performed including all adult cases of bacteremia attributed to SPACE-M species between April 2010 and June 2015 at the McGill University Health Centre (Montreal, Canada). We used multivariable logistic regression to estimate the odds ratio (OR) of death or recurrence within 30 days for potentially hydrolyzable β-lactams vs. other therapies. We then updated a systematic review and meta-analysis comparing carbapenems to β-lactam/β-lactamase inhibitors (BL/BLIs). We included studies published up to December 31, 2017 and calculated the unadjusted OR for mortality within 30 days comparing BL/BLI vs. carbapenems as definitive therapy. Results Over the 5-year period, there were 173 BSI involving SPACE-M organisms at our center. After adjusting for patient comorbidities and severity of the initial illness, the use of hydrolyzable β-lactams as definitive therapy was not associated with an increased risk of death or recurrence when compared with other antimicrobial agents (OR 1.20, 95% CI 0.40–3.62). The meta-analysis further suggested that patients treated with BL/BLI therapy have similar outcomes to those treated with carbapenems (30-day mortality OR 1.13, 95% CI 0.58–2.20). Conclusion The use of β-lactam/β-lactamase inhibitors may remain a viable carbapenem-sparing option for patients with potential AmpC-producing organisms. Disclosures All authors: No reported disclosures.

Background Pyogenic infection with Streptococcus agalactiae is a potentially life-threatening disease associated with significant morbidity and mortality. This type of infection has seldom been reported as a complication of dilation and curettage after an incomplete abortion. Case A young woman presented to the emergency department with rapidly progressive left-sided lower back pain, general malaise, and chills evolving over the previous 48-hours after dilation and curettage for incomplete abortion. Streptococcus agalactiae was isolated in the blood. The patient developed pelvic osteomyelitis despite aggressive medical therapy and required prolonged treatment before significant clinical improvement was noted. Conclusion Although very rare, serious pyogenic complications of dilation and curettage after incomplete abortion do occur and may present a diagnostic challenge.

Diarrhoea still accounts for considerable mortality and morbidity worldwide. The highest burden is concentrated in tropical areas where populations lack access to clean water, adequate sanitation and hygiene. In contrast to acute diarrhoea (14 days), the spectrum of pathogens that may give rise to persistent diarrhoea (≥14 days) and persistent abdominal pain is poorly understood. It is conceivable that pathogens causing neglected tropical diseases play a major role, but few studies investigated this issue. Clinical management and diagnostic work-up of persistent digestive disorders in the tropics therefore remain inadequate. Hence, important aspects regarding the pathogenesis, epidemiology, clinical symptomatology and treatment options for patients presenting with persistent diarrhoea and persistent abdominal pain should be investigated in multi-centric clinical studies.This multi-country, prospective, non-experimental case-control study will assess persistent diarrhoea (≥14 days; in individuals aged ≥1 year) and persistent abdominal pain (≥14 days; in children/adolescents aged 1-18 years) in up to 2000 symptomatic patients and 2000 matched controls. Subjects from Côte d'Ivoire, Indonesia, Mali and Nepal will be clinically examined and interviewed using a detailed case report form. Additionally, each participant will provide a stool sample that will be examined using a suite of diagnostic methods (i.e., microscopic techniques, rapid diagnostic tests, stool culture and polymerase chain reaction) for the presence of bacterial and parasitic pathogens. Treatment will be offered to all infected participants and the clinical treatment response will be recorded. Data obtained will be utilised to develop patient-centred clinical algorithms that will be validated in primary health care centres in the four study countries in subsequent studies.Our research will deepen the understanding of the importance of persistent diarrhoea and related digestive disorders in the tropics. A diversity of intestinal pathogens will be assessed for potential associations with persistent diarrhoea and persistent abdominal pain. Different diagnostic methods will be compared, clinical symptoms investigated and diagnosis-treatment algorithms developed for validation in selected primary health care centres. The findings from this study will improve differential diagnosis and evidence-based clinical management of digestive syndromes in the tropics.ClinicalTrials.gov; identifier: NCT02105714 .

Microscopy has several limitations in the diagnosis of parasitic infection. New technologies have emerged to address some of these limitations. We review recent advances in three key areas. The detection of enteric protozoa is a commonly requested test, particularly with increasing travel to and migration from endemic countries. Microscopy is slow and labor intensive and requires a high level of technical expertise. It also lacks both sensitivity and specificity. Recently developed nucleic acid amplification tests are automated and rapid and show superior accuracy. Proteomics shows promise for both the diagnosis of infections where parasite detection is difficult and the potential for accurate assessment of cure in these cases. Finally, rapid and simple diagnostic tests suitable for use in low-resource settings are now allowing for improved study and control of infection in endemic regions.

The investigation of a N-terminally truncated human transforming growth factor-α (TGF-α; residues 8–50) has been completed to determine the contribution of the N terminus to receptor binding and activation. The deletion protein was proposed and designed through study of NMR relaxation and nuclear Overhauser enhancement data obtained from the TGF-α-epidermal growth factor (EGF) receptor complex, which indicated that the residues N-terminal to the A loop remain flexible in receptor-bound TGF-α and thus suggested their lack of involvement in receptor binding (Hoyt, D. W., Harkins, R. N., Debanne, M. T., O'Connor-McCourt, M., and Sykes, B. D. (1994) Biochemistry 33, 15283–15292; McInnes, C., Hoyt, D. W., Harkins, R. N., Pagila, R. N., Debanne, M. T., O'Connor-McCourt, M., and Sykes, B. D. (1996) J. Biol. Chem. 271, 32204–32211). TGF-α 8–50 was shown to have approximately 10-fold lower affinity for the receptor than the native molecule in an assay quantifying the ability to compete with EGF for binding and to have a similar reduction in activity as indicated by a cell proliferation assay. NMR solution structural calculations on this molecule demonstrate correct formation of the three disulfide bonds of TGF-α 8–50 and have established the presence of native secondary structure in the B and C loops of the protein. However, some perturbation of the global fold with respect to the orientation of the subdomains was observed. These results suggest that although the N-terminal residues do not contribute directly to binding, they make a significant contribution in defining the conformation of the growth factor, which is required for complete binding and activity and is therefore significant in terms of producing native folding of TGF-α. They also show that information obtained from the receptor-bound ligand can be used to guide the design and minimization of TGF-α analogues. The implications of the study of TGF-α 8–50 for the design and synthesis of reductants of this growth factor are therefore discussed.

The genus emmonsia contains three species that are associated with human disease. Emmonsia crescens and Emmonsia parva are the agents that cause adiaspiromycosis, and one human case of Emmonsia pasteuriana infection has been described. We report a fungal pathogen within the genus emmonsia that is most closely related to E. pasteuriana in human immunodeficiency virus (HIV)-infected adults in South Africa.Between July 2008 and July 2011, we conducted enhanced surveillance to identify the cause of systemic, dimorphic fungal infections in patients presenting to Groote Schuur Hospital and other hospitals affiliated with the University of Cape Town, Cape Town, South Africa. DNA sequencing was used to identify pathogenic fungi.A total of 24 cases of dimorphic fungal infection were diagnosed, 13 of which were caused by an emmonsia species. All 13 patients were HIV-infected, with a median CD4+ T-cell count of 16 cells per cubic millimeter (interquartile range, 10 to 44), and all had evidence of disseminated fungal disease. Three patients died soon after presentation, but the others had a good response to a variety of antifungal agents and antiretroviral therapy. Phylogenetic analysis of five genes (LSU, ITS1-2, and the genes encoding actin, β-tubulin, and intein PRP8) revealed that this fungus belongs in the genus emmonsia and is most closely related to E. pasteuriana.The findings suggest that these isolates of an emmonsia species represent a new species of dimorphic fungus that is pathogenic to humans. The species appears to be an important cause of infections in Cape Town.

Severe malaria is a medical emergency requiring early intervention to prevent death. This article highlights key aspects of the management of severe malaria syndromes in the intensive care unit, with a focus on individual case management of imported malaria. Key differences in the presentation, management, and outcomes of severe malaria by endemicity and by age group are emphasized. In all groups with severe malaria, intravenous artesunate is the antimalarial agent of choice. This article discusses specific antimalarial therapies, optimal supportive management strategies, differences from strategies for bacterial sepsis, and trials of adjunctive therapy for severe malaria in humans.

Infections are a leading cause of life-threatening neuropathology worldwide. In central African countries affected by endemic diseases such as human African trypanosomiasis, tuberculosis, HIV/AIDS, and schistosomiasis, delayed diagnosis and treatment often lead to avoidable death or severe sequelae. Confirmatory microbiological and parasitological tests are essential because clinical features of most neurological infections are not specific, brain imaging is seldom feasible, and treatment regimens are often prolonged or toxic. Recognition of this diagnostic bottleneck has yielded major investment in application of advances in biotechnology to clinical microbiology in the past decade. We review the neurological pathogens for which rapid diagnostic tests are most urgently needed in central Africa, detail the state of development of putative rapid diagnostic tests for each, and describe key technical and operational challenges to their development and implementation. Promising field-suitable rapid diagnostic tests exist for the diagnosis of human African trypanosomiasis and cryptococcal meningoencephalitis. For other infections-eg, syphilis and schistosomiasis-highly accurate field-validated rapid diagnostic tests are available, but their role in diagnosis of disease with neurological involvement is still unclear. For others-eg, tuberculosis-advances in research have not yet yielded validated tests for diagnosis of neurological disease.

Background Persistent digestive disorders account for considerable disease burden in the tropics. Despite advances in understanding acute gastrointestinal infections, important issues concerning epidemiology, diagnosis, treatment and control of most persistent digestive symptomatologies remain to be elucidated. Helminths and intestinal protozoa are considered to play major roles, but the full extent of the aetiologic spectrum is still unclear. We provide an overview of pathogens causing digestive disorders in the tropics and evaluate available reference tests. Methods We searched the literature to identify pathogens that might give rise to persistent diarrhoea, chronic abdominal pain and/or blood in the stool. We reviewed existing laboratory diagnostic methods for each pathogen and stratified them by (i) microscopy; (ii) culture techniques; (iii) immunological tests; and (iv) molecular methods. Pathogen-specific reference tests providing highest diagnostic accuracy are described in greater detail. Results Over 30 pathogens may cause persistent digestive disorders. Bacteria, viruses and parasites are important aetiologic agents of acute and long-lasting symptomatologies. An integrated approach, consisting of stool culture, microscopy and/or specific immunological techniques for toxin, antigen and antibody detection, is required for accurate diagnosis of bacteria and parasites. Molecular techniques are essential for sensitive diagnosis of many viruses, bacteria and intestinal protozoa, and are increasingly utilised as adjuncts for helminth identification. Conclusions Diagnosis of the broad spectrum of intestinal pathogens is often cumbersome. There is a need for rapid diagnostic tests that are simple and affordable for resource-constrained settings, so that the management of patients suffering from persistent digestive disorders can be improved.

Objective.The significance of positive cultures of organ preservation fluid (OPF) in solid organ transplantation is not known. We sought to describe the microbiology and define the clinical impact of positive OPF cultures.Design.Retrospective cohort study.Setting.Tertiary care hospital.Patients.A consecutive sample of all solid organ transplantations at our center between July 2006 and January 2009 was reviewed. A total of 331 allografts (185 kidneys, 104 livers, 31 pancreases, and 11 hearts) met the inclusion criterion of having OPF cultures taken from the transplanted allograft.Methods.Organisms recovered from OPF were classified as high or low risk according to their virulence. Clinical outcomes were compared between recipients of organs with positive OPF cultures and recipients of organs with negative OPF cultures.Results.OPF cultures were positive in 62.2% of allografts and yielded high-risk organisms in 17.8%. Normal skin flora constituted the majority of positive OPF cultures, while Enterobacteriaceae spp. andStaphylococcus aureusmade up the majority of high-risk organisms. Recipients of allografts with positive OPF cultures developed more frequent bacterial infections, regardless of allograft type (relative risk, 2.39; 95% confidence interval [CI], 1.61–3.54). Moreover, isolation of a given organism in OPF samples was associated with the development of a clinical infection with the same organism, regardless of allograft type.Conclusions.Positive cultures of OPF are common events in solid organ transplantation, frequently involve high-risk organisms, and are associated with the development of postoperative clinical bacterial infections. Further study is required to determine the optimal strategies for their prevention and management.

Tuberculosis (TB) infection is relatively frequent among travellers to high incidence-countries, especially in long-term travellers and those involved in health work. It is important to diagnose recent infection, both for the affected individual and to prevent further transmission. Based on published literature, we assess the value of interferon-gamma release assays (IGRAs) as a complement to or replacement of the tuberculin skin test (TST) for the diagnosis of latent TB infection in the setting of a travel clinic. A comparison of available IGRAs with the TST in terms of operating characteristics and practical considerations is presented. We conclude that IGRAs offer some practical advantages that may benefit certain well-defined patient groups of a travel clinic, but that current evidence is incomplete. We identify research questions to better define the role of IGRAs in these populations.

Accurate diagnosis of osteomyelitis underlying diabetic foot ulcers is essential to optimize outcomes. We undertook a meta-analysis of the accuracy of diagnostic tests for osteomyelitis in diabetic patients with foot ulcers. Pooled sensitivity and specificity, the summary measure of accuracy (Q*), and diagnostic odds ratio were calculated. Exposed bone or probe-to-bone test had a sensitivity of 0.60 and a specificity of 0.91. Plain radiography had a sensitivity of 0.54 and a specificity of 0.68. MRI had a sensitivity of 0.90 and a specificity of 0.79. Bone scan was found to have a sensitivity of 0.81 and a specificity of 0.28. Leukocyte scan was found to have a sensitivity of 0.74 and a specificity of 0.68. The diagnostic odds ratios for clinical examination, radiography, MRI, bone scan, and leukocyte scan were 49.45, 2.84, 24.36, 2.10, and 10.07, respectively. The presence of exposed bone or a positive probe-to-bone test result is moderately predictive of osteomyelitis. MRI is the most accurate imaging test for diagnosis of osteomyelitis.

The gastrointestinal tract contains a complex mix of microorganisms. Therefore, the finding of a particular microbe in the gastrointestinal tract or stools of a patient with intestinal disease does not necessarily indicate that the clinical state resulted from the presence of this organism. For this reason, extending from epidemiological association to causality is particularly challenging for gastrointestinal diseases. Most established agents of acute bacterial gastroenteritis (eg, Escherichia coli, Campylobacter jejuni) have been shown to fulfil Koch's postulates of causality in human volunteer studies. For Helicobacter pylori, which can cause both acute and chronic disease, the organism was first linked to an acute syndrome through volunteer studies and then later assessed for a role in chronic disease by use of Hill's epidemiological criteria of causation. However, for agents of chronic intestinal disease, this approach is not ethical and risks overlooking events occurring long after the exposure. We examine the criteria used to judge causality (Koch's postulates and Hill's criteria) and their applicability for chronic gastrointestinal diseases (eg, Whipple's disease and Crohn's disease). We also identify crucial research questions required to advance towards assessing the causal role of candidate microbes in the aetiopathogenesis of Crohn's disease.

The detection of schistosomiasis cases among Belgian military personnel returning from a mission in the Democratic Republic of Congo (DRC) prompted a nested case-control study of all military personnel deployed in the DRC between 2005 and 2008 to identify all infections and to start appropriate treatment. Of 197 patients exposed at Lake Tanganyika in the Kalemie area of DRC, 49 (24.9%) were diagnosed with schistosomiasis. Swimming was significantly more frequent than wading in the seropositive group than in the seronegative group (88.9% vs. 73.6%; odds ratio [OR], 2.86; 95% confidence interval [CI], 0.97-9.01). Thirty-one of 49 patients (63.3%) were symptomatic; including skin problems in 34.7%, respiratory symptoms in 12.2%, fever in 14.3%, and 51.0% with gastrointestinal problems. Median eosinophil counts were significantly higher in seropositive patients (375 vs. 138 per tL; Wilcoxon rank sum test [Ws] = 10,559.00; p0.01; r = -0.49). In total, 20 (40.8%) of the 49 patients were treated for symptomatic infections and the remainder for asymptomatic schistosomiasis. Our study emphasizes the need for active systematic post-tropical screening in military personnel after deployment to Schistosoma-endemic regions of the world.

Background In light of the 2016 summer Olympic games it is anticipated that Canadian practitioners will require information about common illnesses that may affect travellers returning from Brazil. Objective To identify the demographic and travel correlates of illness among recent Canadian travellers and migrants from Brazil attending a network of travel health clinics across Canada. Methods Data was analyzed on returned Canadian travellers and migrants presenting to a CanTravNet site for care of an illness between June 2013 and June 2016. Results During the study period, 7,707 ill travellers and migrants presented to a CanTravNet site and 89 (0.01%) acquired their illness in Brazil. Tourists were most well represented (n=45, 50.6%), followed by those travelling to "visit friends and relatives" (n=14, 15.7%). The median age was 37 years (range