Using a family history questionnaire to identify adult patients with increased genetic risk for sarcoma.

BACKGROUND: Sarcomas in adults can be associated with hereditary cancer syndromes characterized by early-onset predisposition to numerous types of cancer. Because of variability in familial presentation and the largely unexplained genetic basis of sarcomas, ascertainment of patients for whom a genetics evaluation is most indicated poses challenges. We assessed the utility of a Sarcoma Clinic Genetic Screening (scgs) questionnaire in facilitating that task. METHODS: Between 2008 and 2012, 169 patients (median age: 53 years; range: 17-88 years) completed a self-administered scgs questionnaire. A retrospective chart review was completed for all respondents, and descriptive statistics were reported. Probands were divided into two groups depending on whether they did or did not report a family history of Li-Fraumeni syndrome-type cancers. RESULTS: A family history of cancer (as far as 3rd-degree relatives) was reported in 113 of 163 sarcoma patients (69%). Eeles Li-Fraumeni-like (lfl) criteria were fulfilled in 46 probands (28%), Chompret lfl in 21 (13%), Birch lfl in 8 (5%), and classic Li-Fraumeni in none. In the 10 probands tested for TP53 mutations, 1 pathogenic mutation was found. Further investigation of selected families led to the discovery of germline mutations in MLH1, MSH2, and APC genes in 3 individuals. CONCLUSIONS: The scgs questionnaire was useful for ascertaining probands with sarcoma who could benefit from a genetic assessment. The tool allowed us to identify high-risk families fitting the criteria for lfl and, surprisingly, other hereditary cancer syndromes. Similar questionnaires could be used in other cancer-specific clinics to increase awareness of the genetic component of these cancers.

Public health approach to detection of non-O157 Shiga toxin-producing Escherichia coli: summary of two outbreaks and laboratory procedures.

Routine laboratory testing may not detect non-O157 Shiga toxin-producing Escherichia coli (STEC) reliably. Active clinical, epidemiological, environmental health, and laboratory collaboration probably influence successful detection and study of non-O157 STEC infection. We summarized two outbreak investigations in which such coordinated efforts identified non-O157 STEC disease and led to effective control measures. Outbreak 1 involved illness associated with consuming unpasteurized apple cider from a local orchard. Public health personnel were notified by a local hospital; stool specimens from ill persons contained O111 STEC. Outbreak 2 involved bloody diarrhoea at a correctional facility. Public health personnel were notified by the facility infection control officer; O45 STEC was the implicated agent. These reports highlight the ability of non-O157 STEC to cause outbreaks and demonstrate that a coordinated effort by clinicians, infection-control practitioners, clinical diagnostic laboratorians, and public health personnel can lead to effective identification, investigation, and prevention of non-O157 STEC disease.

Multistate outbreak of Escherichia coli O157:H7 infections associated with a national fast-food chain, 2006: a study incorporating epidemiological and food source traceback results.

A multistate outbreak of Escherichia coli O157:H7 infections occurred in the USA in November-December 2006 in patrons of restaurant chain A. We identified 77 cases with chain A exposure in four states - Delaware, New Jersey, New York, and Pennsylvania. Fifty-one (66%) patients were hospitalized, and seven (9%) developed haemolytic uraemic syndrome; none died. In a matched analysis controlling for age in 31 cases and 55 controls, illness was associated with consumption of shredded iceberg lettuce [matched odds ratio (mOR) 8·0, 95% confidence interval (CI) 1·1-348·1] and shredded cheddar cheese (mOR 6·2, CI 1·7-33·7). Lettuce, an uncooked ingredient, was more commonly consumed (97% of patients) than cheddar cheese (84%) and a single source supplied all affected restaurants. A single source of cheese could not explain the regional distribution of outbreak cases. The outbreak highlights challenges in conducting rapid multistate investigations and the importance of incorporating epidemiological study results with other investigative findings.

The prevalence of multidrug resistance is higher among bovine than human Salmonella enterica serotype Newport, Typhimurium, and 4,5,12:i:- isolates in the United States but differs by serotype and geographic region.

Salmonella represents an important zoonotic pathogen worldwide, but the transmission dynamics between humans and animals as well as within animal populations are incompletely understood. We characterized Salmonella isolates from cattle and humans in two geographic regions of the United States, the Pacific Northwest and the Northeast, using three common subtyping methods (pulsed-field gel electrophoresis [PFGE], multilocus variable number of tandem repeat analysis [MLVA], and multilocus sequence typing [MLST]). In addition, we analyzed the distribution of antimicrobial resistance among human and cattle Salmonella isolates from the two study areas and characterized Salmonella persistence on individual dairy farms. For both Salmonella enterica subsp. enterica serotypes Newport and Typhimurium, we found multidrug resistance to be significantly associated with bovine origin of isolates, with the odds of multidrug resistance for Newport isolates from cattle approximately 18 times higher than for Newport isolates from humans. Isolates from the Northwest were significantly more likely to be multidrug resistant than those from the Northeast, and susceptible and resistant isolates appeared to represent distinct Salmonella subtypes. We detected evidence for strain diversification during Salmonella persistence on farms, which included changes in antimicrobial resistance as well as genetic changes manifested in PFGE and MLVA pattern shifts. While discriminatory power was serotype dependent, the combination of PFGE data with either MLVA or resistance typing data consistently allowed for improved subtype discrimination. Our results are consistent with the idea that cattle are an important reservoir of multidrug-resistant Salmonella infections in humans. In addition, the study provides evidence for the value of including antimicrobial resistance data in epidemiological investigations and highlights the benefits and potential problems of combining subtyping methods.

Salmonella enterica serotype 4,5,12:i:-, an emerging Salmonella serotype that represents multiple distinct clones.

The prevalence, among human clinical cases, of Salmonella enterica serotype 4,5,12:i:-, a serotype antigenically similar to Salmonella enterica serotype Typhimurium but lacking second-phase flagellar antigens, has increased considerably over the last 10 years. To probe the evolution and ecology of this emerging serotype, we characterized 190 Salmonella isolates initially classified as Salmonella serotypes 4,5,12:i:- (n = 90) and Typhimurium (n = 100) and obtained from various sources in the United States and Spain. These isolates were characterized into six sequence types (determined by multilocus sequence typing [MLST]) and 79 pulsed-field gel electrophoresis types. The majority of Salmonella serotype 4,5,12:i:- and Typhimurium isolates (85 and 84 isolates, respectively) represented a single MLST type. Existing genome information revealed different genome deletions (which included genes responsible for phase 2 flagellum expression) in four Spanish Salmonella serotype 4,5,12:i:- isolates and one U.S. Salmonella serotype 4,5,12:i:- isolate. Fifty-nine isolates of both serotypes, representing different sources and geographical locations as well as different molecular subtypes, were thus screened for the presence of six genes and one specific region, all of which were previously found to show variable presence among Salmonella serotype 4,5,12:i:- and Typhimurium strains. All Salmonella serotype 4,5,12:i:- isolates lacked the phase 2 flagella genes fljA and fljB, which were present in all Salmonella serotype Typhimurium isolates. While all Spanish Salmonella serotype 4,5,12:i:- isolates carried the same deletion surrounding fljAB, all but two U.S. isolates showed a different genomic deletion; the two atypical U.S. isolates represented the "Spanish" deletion genotype and a unique deletion genotype. Salmonella serotype 4,5,12:i:- thus appears to represent at least two common clones, which cannot easily be differentiated with standard diagnostic procedures.

The Quebec experience in promoting healthy lifestyles and preventing obesity: how can we do better?

Over the last years, many actions have been implemented in the Canadian province of Quebec to prevent health issues related to diet, physical activity and obesity. As a new public health programme is being launched, the 'How can we do better?' project aimed to identify priority areas for further action. An exhaustive search led to identify 166 interventions rolled out in Quebec between 2006 and 2014. We compared it with evidence-based recommendations. Findings were challenged during a 2-d deliberative forum gathering 25 key stakeholders. At the crossroads of these analyses, 50 proposals emerged to sustain/bolster current efforts or to implement new initiatives. Specific improvements were recommended, e.g. about food supply quality monitoring, healthy food accessibility and affordability, physical activity promotion through land use policies, schools and childcare facilities retrofit and urban planning. Crosscutting proposals stress the importance to implement a new governmental prevention strategy and to reinforce evaluation at all levels. This call for action takes place at a critical period for political commitment and should be maintained until and after curbing the prevalence of obesity and related diseases. Although Quebec-focused, 'How can we do better?' project outcomes may be informative for other jurisdictions, and the methods may be inspiring for those interested in combining knowledge syntheses and deliberative processes to inform decision makers in a limited time frame.

Human cytosolic sulfotransferase 2B1: isoform expression, tissue specificity and subcellular localization.

Sulfation is an important Phase II conjugation reaction involved in the synthesis and metabolism of steroids in humans. Two different isoforms (2B1a and 2B1b) are encoded by the sulfotransferase (SULT) 2B1 gene utilizing different start sites of transcription resulting in the incorporation of different first exons. SULT2B1a and SULT2B1b are 350 and 365 amino acids in length, respectively, and the last 342 aa are identical. Message for both SULT2B1 isoforms is present in human tissues although SULT2B1b message is generally more abundant. However, to date only SULT2B1b protein has been detected in human tissues or cell lines. SULT2B1b is localized in the cytosol and/or nuclei of human cells. A unique 3'-extension of SULT2B1b is required for nuclear localization in human BeWo placental choriocarcinoma cells. Nuclear localization is stimulated by forskolin treatment in BeWo cells and serine phosphorylation has been identified in the 3'-extension. SULT2B1b is selective for the sulfation of 3beta-hydroxysteroids such as dehydroepiandrosterone and pregnenolone, and may also have a role in cholesterol sulfation in human skin. The substrate specificity, nuclear localization, and tissue localization of SULT2B1b suggest a role in regulating the responsiveness of cells to adrenal androgens via their direct inactivation or by preventing their conversion to more potent androgens and estrogens.

[Latex agglutination reaction for the diagnosis of toxoplasmosis]. / Etude d'une réaction d'agglutination au latex pour le diagnostic de la toxoplasmose.

Agglutination of latex-particles sensitized with toxoplasma-antigen is a simple, fast, inexpensive test for toxoplasmosis-diagnosis. This test has been compared with passive-hemagglutination (1091 sera) and immunofluorescence (1093 sera). From the results, this new test is showed to be closer to passive-hemagglutination than indirect immunofluorescence. After studying possible false results and biological qualities it is thought that this test has good qualities to render great services for the toxoplasmosis diagnosis, and specially for epidemiological investigations.

[Epidemiology of toxoplasmosis in mothers and children in tropical Africa]. / Epidémiologie de la toxoplasmose chez la mère et l'enfant en Afrique tropicale.

The purpose of this study was the epidemiology of toxoplasmosis in Congo, Ivory Coast (IC), Niger, Centrafrican Republic, Zaïre. This statistical study was relied upon the search of IgG and IgM antibodies. In Niger, the risk connected with the first contact of the parasite was very low for children and young women, since only 2.6% of children under 15 years were carrying IgG and 5.4% of women between 15 and 30. In the other countries, the highest risk of first contact occurred before reaching 10 years and mostly between 5 and 9 (the IgG survey was confirmed by IgM survey). Nevertheless, IgM survey had indicated that for the young women there was a risk of first contact until reaching 20 years in IC and 30 years in Congo. A comparative study of antibodies developed among the couple mother-children was conducted in IC and Congo.

[Toxoplasmosis in the Central African Republic. Complementary study in a rural area]. / La toxoplasmose en République centrafricaine (RCA). Etude complémentaire en zone rurale.

The epidemiological survey on the incidence of toxoplasmosis in rural areas of Central African Republic was carried out on a healthy population. The 814 samples came from 5 regions with 4 different climates. About 40% of the adults had IgG antibodies against Toxoplasma gondii except in pre-desert area where only 25% were positive. Girls became positive earlier than boys, but there was no difference between adult men and women except in pre-desert zone where men were more positive.

[Toxoplasmosis in the Congo Republic. Seroepidemiological study]. / La toxoplasmose en République du Congo. Etude séroépidémiologique.

Our study group, which was composed of over 2,500 subjects, aged between 0 and 65 years, came from different regions of Congo. The samples obtained were examined for the presence of IgG and IgM against Toxoplasma gondii. IgG were detected in about 33% of children over 9 years and in about 40% of adults. A study of IgM confirmed the early contact of children with the parasite (11% of positive samples for children between 4 and 9) and that of young women (5 to 7% positivity for subjects between 15 and 30). In spite of local variations, the extremely humid climate did not allow us to detect a difference based on the origin of the samples as furthermore there seems to be an ethnic factor involved. Among the different types of professions in our sample only farmers appear to be less frequently positive. Diet, as well as contact with animals do not seem to have an influence.

Antimicrobial drug resistance patterns among cattle- and human-associated Salmonella strains.

During the year 2004, 178 human and 158 bovine clinical Salmonella isolates were collected across New York State to better understand the transmission dynamics and genetic determinants of antimicrobial resistance among human and bovine hosts. Serotyping, sequence typing, and pulsed-field gel electrophoresis typing results have been reported previously. Here we tested all isolates for phenotypic susceptibility to 15 antimicrobial drugs that are part of the National Antimicrobial Monitoring System bovine susceptibility panel. PCR was performed on a representative subset of unique isolates (n = 53) to screen for the presence of 21 known antimicrobial resistance genes (i.e., ampC, blaTEM-1, blaCMY-2, blaPSE-1, cat1, cat2, cmlA, flo, aadA1, aadA2, aacC2, strA, strB, aphA1-IAB, dhrfI, dhrfXII, sulI, sulII, tetA, tetB, and tetG); selected fluoroquinolone- and nalidixic acid-resistant (n = 3) and -sensitive (n = 6) isolates were also tested for known resistance-conferring mutations in gyrA and parC. Genes responsible for antimicrobial resistance were shared among isolates of human and bovine origin. However, bovine isolates were significantly more likely than human isolates to be multidrug resistant (P < 0.0001; Fisher's exact test). Our analyses showed perfect categorical agreement between phenotypic and genotypic resistance for beta-lactam and chloramphenicol. Our data confirm that resistance profiles of amoxicillin-clavulanic acid, chloramphenicol, kanamycin, and tetracycline were strongly associated with the presence of blaCMY or ampC, flo, aphA1-IAB, and tetA, respectively. Our findings provide evidence for the clinical value of genotypic resistance typing if incorporating multiple known genes that can confer a phenotypic resistance profile.

Salmonella Cerro isolated over the past twenty years from various sources in the US represent a single predominant pulsed-field gel electrophoresis type.

Salmonella Cerro prevalence in US dairy cattle has increased significantly during the past decade. Comparison of 237 Salmonella isolates collected from various human and animal sources between 1986 and 2009 using pulsed-field gel electrophoresis, antimicrobial resistance typing, and spvA screening, showed very limited genetic diversity, indicating clonality of this serotype. Improved subtyping methods are clearly needed to analyze the potential emergence of this serotype. Our results thus emphasize the critical importance of population-based pathogen surveillance for the detection and characterization of potentially emerging pathogens, and caution to critically evaluate the adequacy of diagnostic tests for a given study population and diagnostic application.

Multilocus sequence typing supports the hypothesis that cow- and human-associated Salmonella isolates represent distinct and overlapping populations.

A collection of 179 human and 156 bovine clinical Salmonella isolates obtained from across New York state over the course of 1 year was characterized using serotyping and a multilocus sequence typing (MLST) scheme based on the sequencing of three genes (fimA, manB, and mdh). The 335 isolates were differentiated into 52 serotypes and 72 sequence types (STs). Analyses of bovine isolates collected on different farms over time indicated that specific subtypes can persist over time on a given farm; in particular, a number of farms showed evidence for the persistence of a specific Salmonella enterica serotype Newport sequence type. Serotypes and STs were not randomly distributed among human and bovine isolates, and selected serotypes and STs were associated exclusively with either human or bovine sources. A number of common STs were geographically widespread. For example, ST6, which includes isolates representing serotype Typhimurium as well as the emerging serotype 4,5,12:i:-, was found among human and bovine isolates in a number of counties in New York state. Phylogenetic analyses supported the possibility that serotype 4,5,12:i:- is closely related to Salmonella serotype Typhimurium. Salmonella serotype Newport was found to represent two distinct evolutionary lineages that differ in their frequencies among human and bovine isolates. A number of Salmonella isolates carried two copies of manB (33 isolates) or showed small deletion events in fimA (nine isolates); these duplication and deletion events may provide mechanisms for the rapid diversification of Salmonella surface molecules. We conclude that the combined use of an economical three-gene MLST scheme and serotyping can provide considerable new insights into the evolution and transmission of Salmonella.

[Rickettsiosis and chlamydiosis in Hoggar (Republic of Algeria): epidemiological sampling]. / Rickettsioses et chlamydioses au Hoggar (République Algérienne): sondage épidémiologique.

The study was made on reservoirs of infections (rodent, sheep, goat, dromedary), vectors (louse) and human-receptors. Examinations were made on smears examined with staining and indirect-fluorescente techniques and on sera examined by complement fixation test. Chlamydia psittaci appears very often in rodent, sheep, goat, dromedary and man. Antibodies against Coxiella burneti were found present in sheep, goat but mainly in dromedary and less than 16 years old boys. Two lice were carrier of Rickettsia prowazeki; Rickettsia mooseri was detected on one louse and one mouse.