Michael Libman

GeoSentinel surveillance of illness in returned travelers, 2007-2011.

BACKGROUND International travel continues to increase, particularly to Asia and Africa. Clinicians are increasingly likely to be consulted for advice before travel or by ill returned travelers. OBJECTIVE To describe typical diseases in returned travelers according to region, travel reason, and patient demographic characteristics; describe the pattern of low-frequency travel-associated diseases; and refine key messages for care before and after travel. DESIGN Descriptive, using GeoSentinel records. SETTING 53 tropical or travel disease units in 24 countries. PATIENTS 42 173 ill returned travelers seen between 2007 and 2011. MEASUREMENTS Frequencies of demographic characteristics, regions visited, and illnesses reported. RESULTS Asia (32.6%) and sub-Saharan Africa (26.7%) were the most common regions where illnesses were acquired. Three quarters of travel-related illness was due to gastrointestinal (34.0%), febrile (23.3%), and dermatologic (19.5%) diseases. Only 40.5% of all ill travelers reported pretravel medical visits. The relative frequency of many diseases varied with both travel destination and reason for travel, with travelers visiting friends and relatives in their country of origin having both a disproportionately high burden of serious febrile illness and very low rates of advice before travel (18.3%). Life-threatening diseases, such as Plasmodium falciparum malaria, melioidosis, and African trypanosomiasis, were reported. LIMITATIONS Sentinel surveillance data collected by specialist clinics do not reflect healthy returning travelers or those with mild or self-limited illness. Data cannot be used to infer quantitative risk for illness. CONCLUSION Many illnesses may have been preventable with appropriate advice, chemoprophylaxis, or vaccination. Clinicians can use these 5-year GeoSentinel data to help tailor more efficient pretravel preparation strategies and evaluate possible differential diagnoses of ill returned travelers according to destination and reason for travel. PRIMARY FUNDING SOURCE Centers for Disease Control and Prevention.

The epidemiology of peripheral vein infusion thrombophlebitis: a critical review

We critically assessed studies on the clinical importance, diagnosis, incidence, and pathogenesis of peripheral vein infusion thrombophlebitis, including catheter-related and patient-related risk factors. We reviewed the evidence linking thrombosis, particularly prothrombotic states such as the inherited thrombophilic disorders, with peripheral vein infusion thrombophlebitis. Peripheral vein infusion thrombophlebitis occurs in 25% to 35% of hospitalized patients with peripheral intravenous catheters and has both patient-related implications (e.g., sepsis) and economic consequences (e.g., extra nursing time). Although duration of catheterization, catheter-related infection, and catheter material are important risk factors for peripheral vein infusion thrombophlebitis, patient-related risk factors are not well elucidated.

Predictors of inappropriate antibiotic prescribing among primary care physicians

Background: Inappropriate use of antibiotics promotes antibiotic resistance. Little is known about physician characteristics that may be associated with inappropriate antibiotic prescribing. Our objective was to assess whether physician knowledge, time in practice, place of training and practice volume explain the differences in antibiotic prescribing among physicians. Methods: A historical cohort of 852 primary care physicians in Quebec who became certified between 1990 and 1993 was followed for their first 6–9 years of practice (1990–1998). We evaluated whether inappropriate antibiotic prescribing had occurred during the study period (1990–1998) for viral (prescription of antibiotics) and bacterial (prescription of second-or third-line antibiotics given orally) infections. We used logistic regression to estimate the independent contributions of time in practice, practice volume, place of medical training and scores on licensure examinations. Physician sex and visit setting were controlled for, as were patient age, sex, education, income and geographic area of residence. Results: A total of 104 230 patients who received a diagnosis of a viral infection and 65 304 who received a diagnosis of a bacterial infection were included in our study. International medical graduates were more likely than University of Montréal graduates to prescribe antibiotics for viral respiratory infections (risk ratio [RR] 1.78, 95% confidence interval [CI] 1.30–2.44). Inappropriate antibiotic prescribing increased with time in practice. Physicians with a high practice volume were more likely than those with low practice volume to prescribe antibiotics for viral respiratory infections (RR 1.27, 95% CI 1.09–1.48) and to prescribe second-and third-line antibiotics as first-line treatment (RR 1.20, 95% CI 1.06–1.37). Physician scores on licensure examinations were not predictive of inappropriate antibiotic prescribing. Interpretation: International medical graduates, physicians with high-volume practices and those who were in practice longer were more likely to prescribe antibiotics inappropriately. Developing effective interventions will require increased knowledge of the mechanisms that underlie these predictors of inappropriate antibiotic prescribing.

Epidemiology and antifungal susceptibility of bloodstream Candida isolates in Quebec: Report on 453 cases between 2003 and 2005

BACKGROUND Between May 2003 and April 2005, a population-based surveillance of Candida bloodstream infections was conducted in Quebec. A total of 453 episodes of candidemia (464 yeast isolates) from 54 participating hospitals were studied. RESULTS The annual incidence rate was three per 100,000 population. Global hospital mortality was 38%. The most common predisposing factors were the presence of an intravascular catheter (80%), use of antibacterial therapy (67%), stay in an intensive care unit (49%), use of parenteral nutrition (32%) and intra-abdominal surgery (31%). Fluconazole alone or in association with other antifungals was used for treatment in over 80% of cases. Candida albicans comprised 62% of isolates, followed by Candida glabrata (17%), Candida parapsilosis (9%), Candida tropicalis (5%), Candida lusitaniae (3%) and Candida krusei (3%). Of the 288 C albicans isolates, seven (2%) were resistant to flucytosine, one to fluconazole and none to itraconazole or voriconazole. Of the 75 non-C albicans species isolates with reduced susceptibility to fluconazole (minimum inhibitory concentration [MIC] 16 mug/mL or greater), none were susceptible to itraconazole (MIC 0.12 mg/L or lower), whereas 71 (95%) were susceptible to voriconazole (MIC 1 mug/mL or lower). However, only five of 12 (42%) fluconazole-resistant isolates were susceptible to voriconazole. Posaconazole, ravuconazole and caspofungin displayed a broad spectrum of activity against these isolates, with MICs of 1 mg/L or lower in 56%, 92% and 100% of isolates, respectively. Overall, a correlation (r(2)>0.87) was observed among increasing fluconazole MICs and the geometric mean MICs of itraconazole, voriconazole, posaconazole and ravuconazole. CONCLUSIONS These surveillance results when compared with those of the 1993 to 1995 survey confirm little variation in the distribution of species causing invasive Candida infection over a 10-year period in Quebec, as well as the continuous excellent overall in vitro activity of fluconazole.

Seroprevalence of Toxoplasma gondii among Nunavik Inuit (Canada).

As a result of their intimate contact with the land and their nutritional habits, the Inuit of Nunavik are considered to be at risk from zoonotic infections. To better understand the risk factors for Toxoplasma gondii infection, a serosurvey was conducted in Nunavik, Québec, in September 2004. A representative sample of the Inuit adult population of Nunavik participated in this cross‐sectional study (n = 917). Antibodies (IgG) against T. gondii were detected by immunoassay. Information on sociodemographic characteristics, traditional activities, domestic environment and nutrition was gathered by questionnaire and explored as variables explanatory of seropositive results. Associations found to be statistically significant in univariate analyses were assessed by multivariable logistic regression to control for confounding factors. Almost two thirds (59.8%) of the Inuit of Nunavik were found to be seropositive for T. gondii. In multivariate analyses, risk factors for seropositivity were: increasing age, gender (women > men), lower level of education, consumption of potentially contaminated water (determined by an index of risk from waterborne infections), frequent cleaning of water reservoirs, and consumption of seal meat and feathered game. There was some variation in seroprevalence between the Ungava Bay coast (52.3%) and the Hudson Bay coast (65.6%), the two main regions of Nunavik, but this variation was not significant in the multivariable logistic regression model. This cross‐sectional study demonstrated high T. gondii seroprevalence in the Inuit population and revealed that age, gender, schooling and community of residence all influence serostatus in this population. Variables related to drinking water and food choices may also influence the risk of infection. These results raise important questions about T. gondii transmission in Nunavik including possible links between terrestrial and marine cycles.

Seizure vs. syncope: measuring serum creatine kinase in the emergency department.

Objective:To determine the utility of serum creatine kinase measurement for diagnosing generalized tonic-clonic seizures in patients presenting to an emergency department with transient loss of consciousness.Design:Prospective evaluation of a diagnostic parameter. Retrospective data collection with blinded assignment to diagnostic groups.Setting:University teaching hospital.Patients:Sequential sample of 205 patients with transient loss of consciousness. The study group consisted of 96 patients who had creatine kinase measurements in the emergency department.Measurements and main results:An investigator blinded to the results of creatine kinase measurements retrospectively classified events into seizure and nonseizure groups on the basis of clinical presentation, prior history, and follow-up investigations. Mean (±SE) creatine kinase level was significantly higher in the seizure group (231.1±34.8 U/L vs. 70.5±5.6 U/L, p<0.001). Elevated creatine kinase had a test specificity of 0.98 (95% CI 0.90–1.00) and a sensitivity of 0.43 (95% CI 0.28–0.59). The discriminating power of creatine kinase elevation was directly related to the time interval between the event and testing (p<0.0001). Among samples taken more than three hours after the event, test sensitivity was 0.80 (0.52–1.00) and specificity was 0.94 (0.71–1.00).Conclusion:Creatine kinase may be a useful test for evaluating patients with transient loss of consciousness. The test is highly specific for diagnosing generalized seizures in the emergency department. Test sensitivity improves by sampling serum at least three hours after the event.

Mid-trimester maternal plasma cytokines and CRP as predictors of spontaneous preterm birth.

Most previous studies of maternal cytokines and preterm birth have analyzed immunologic biomarkers after the onset of labor or membrane rupture; fewer have examined the systemic (blood) immune response prior to labor onset. We carried out a case-control study nested in a large (n=5337) prospective, multi-center cohort. Cohort women had an interview, examination, and venipuncture at 24-26 weeks. Frozen plasma samples in women with spontaneous preterm birth (n=207) and approximately 2 term controls per case (n=444) were analyzed using Luminex multianalyte profiling technology. Fresh placentas were fixed, stained, and blindly assessed for histologic evidence of infection/inflammation, decidual vasculopathy, and infarction, and vaginal swabs were analyzed for bacterial vaginosis and fetal fibronectin concentration. High maternal matrix metalloproteinase-9 (MMP-9) concentration, but none of the other cytokines or C-reactive protein (CRP), was significantly associated with spontaneous preterm birth [adjusted OR=1.7 (1.1-2.4)] and showed a dose-response relation across quartiles. No association was observed, however, between maternal MMP-9 and placental infection/inflammation, bacterial vaginosis, or vaginal fetal fibronectin concentration. Our results require confirmation in future studies but suggest that a systemic immune response implicating MMP-9 may have an etiologic role in spontaneous preterm birth.

Seroprevalence of Seven Zoonotic Infections in Nunavik, Quebec (Canada)

In Nunavik, common practices and food habits such as consumption of raw meat and untreated water place the Inuit at risk for contracting zoonotic diseases. The aim of this study was to determine the seroprevalence of seven zoonotic infections among the permanent residents of Nunavik. The study was conducted in the fall 2004 as part of the Nunavik Health Survey. Blood samples from adults aged 18–74 years (n = 917) were collected and analysed for the presence of antibodies against Trichinella spp., Toxocara canis, Echinococcus granulosus, Brucella spp., Coxiella burnetii, Leptospira spp. and Francisella tularensis. Information on sociodemographic characteristics, traditional activities, drinking water supply and nutrition was gathered using english/inuktitut bilingual questionnaires. The chi‐squared test was used to evaluate associations between seropositivity and other measured variables. Statistically significant variables were included in a multivariate logistic regression model to control for confounding factors. Estimated seroprevalences were 8.3% for E. granulosus, 3.9% for T. canis, 5.9% for Leptospira spp. and 18.9% for F. tularensis. Seroprevalence was ≤1% for Trichinella spiralis, Brucella spp. and C. burnetii. For most infections, seropositivity tended to increase with age. In multivariate analyses, seroprevalence was positively (i.e. directly) associated with age and residence in the Ungava coast area for F. tularensis; age and residence in the Hudson coast area for T. canis; female gender, lower level of schooling and frequent cleaning of water reservoirs for E. granulosus. No risk factor for Leptospira spp. infection was identified. No associations were detected with regards to food habits or environmental exposures. A small but significant portion of the Nunavik population has serologic evidence of exposure to at least one of the pathogenic microorganisms investigated. Further studies are needed to better understand the mechanisms for transmission of zoonotic infections and their potential reservoirs in Nunavik.

Travel-associated Zika virus disease acquired in the americas through February 2016: A GeoSentinel analysis

Background Zika virus has spread rapidly in the Americas and has been imported into many nonendemic countries by travelers. Objective To describe clinical manifestations and epidemiology of Zika virus disease in travelers exposed in the Americas. Design Descriptive, using GeoSentinel records. Setting 63 travel and tropical medicine clinics in 30 countries. Patients Ill returned travelers with a confirmed, probable, or clinically suspected diagnosis of Zika virus disease seen between January 2013 and 29 February 2016. Measurements Frequencies of demographic, trip, and clinical characteristics and complications. Results Starting in May 2015, 93 cases of Zika virus disease were reported. Common symptoms included exanthema (88%), fever (76%), and arthralgia (72%). Fifty-nine percent of patients were exposed in South America; 71% were diagnosed in Europe. Case status was established most commonly by polymerase chain reaction (PCR) testing of blood and less often by PCR testing of other body fluids or serology and plaque-reduction neutralization testing. Two patients developed Guillain-Barré syndrome, and 3 of 4 pregnancies had adverse outcomes (microcephaly, major fetal neurologic abnormalities, and intrauterine fetal death). Limitation Surveillance data collected by specialized clinics may not be representative of all ill returned travelers, and denominator data are unavailable. Conclusion These surveillance data help characterize the clinical manifestations and adverse outcomes of Zika virus disease among travelers infected in the Americas and show a need for global standardization of diagnostic testing. The serious fetal complications observed in this study highlight the importance of travel advisories and prevention measures for pregnant women and their partners. Travelers are sentinels for global Zika virus circulation and may facilitate further transmission. Primary Funding Source Centers for Disease Control and Prevention, International Society of Travel Medicine, and Public Health Agency of Canada.

Patterns of Illness in Travelers Visiting Mexico and Central America: The GeoSentinel Experience

BACKGROUND Mexico and Central America are important travel destinations for North American and European travelers. There is limited information on regional differences in travel related morbidity. METHODS We describe the morbidity among 4779 ill travelers returned from Mexico and Central America who were evaluated at GeoSentinel network clinics during December 1996 to February 2010. RESULTS The most frequent presenting syndromes included acute and chronic diarrhea, dermatologic diseases, febrile systemic illness, and respiratory disease. A higher proportion of ill travelers from the United States had acute diarrhea, compared with their Canadian and European counterparts (odds ratio, 1.9; P < .0001). During the 2009 H1N1 influenza outbreak from March 2009 through February 2010, the proportionate morbidity (PM) associated with respiratory illnesses in ill travelers increased among those returned from Mexico, compared with prior years (196.0 cases per 1000 ill returned travelers vs 53.7 cases per 1000 ill returned travelers; P < .0001); the PM remained constant in the rest of Central America (57.3 cases per 1000 ill returned travelers). We identified 50 travelers returned from Mexico and Central America who developed influenza, including infection due to 2009 H1N1 strains and influenza-like illness. The overall risk of malaria was low; only 4 cases of malaria were acquired in Mexico (PM, 2.2 cases per 1000 ill returned travelers) in 13 years, compared with 18 from Honduras (PM, 79.6 cases per 1000 ill returned travelers) and 14 from Guatemala (PM, 34.4 cases per 1000 ill returned travelers) during the same period. Plasmodium vivax malaria was the most frequent malaria diagnosis. CONCLUSIONS Travel medicine practitioners advising and treating travelers visiting these regions should dedicate special attention to vaccine-preventable illnesses and should consider the uncommon occurrence of acute hepatitis A, leptospirosis, neurocysticercosis, acute Chagas disease, onchocerciasis, mucocutaneous leishmaniasis, neurocysticercosis, HIV, malaria, and brucellosis.