Detecting national human enteric disease outbreaks linked to animal contact in the United States of America.

Enteric pathogens, such as non-typhoidal Salmonella, Campylobacter and Escherichia coli, can reside in the intestinal tract of many animals, including livestock, companion animals, small mammals and reptiles. Often, these animals can appear healthy; nonetheless, humans can become infected after direct or indirect contact, resulting in a substantial illness burden. An estimated 14% of the 3.2 million illnesses that occur in the United States of America (USA) each year from such enteric pathogens are attributable to animal contact. Surveillance for enteric pathogens in the USA includes the compilation and interpretation of both laboratory and epidemiologic data. However, the authors feel that a collaborative, multisectoral and transdisciplinary - or One Health - approach is needed for data collection and analysis, at every level. In addition, they suggest that the future of enteric illness surveillance lies in the development of improved technologies for pathogen detection and characterisation, such as genomic sequencing and metagenomics. In particular, using whole-genome sequencing to compare genetic sequences of enteric pathogens from humans, food, animals and the environment, can help to predict antimicrobial resistance among these pathogens, determine their genetic relatedness and identify outbreaks linked to a common source. In this paper, the authors describe three recent, multi-state human enteric illness outbreaks linked to animal contact in the USA and discuss how integrated disease surveillance was essential to outbreak detection and response. Additional datasharing between public health and animal health laboratories and epidemiologists at the local, national, regional and international level may help to improve surveillance for emerging animal and human health threats and lead to new opportunities for prevention.

Les agents pathogènes entériques tels que les Salmonella non typhiques, Campylobacter et Escherichia coli peuvent coloniser le tractus intestinal d'un grand nombre d'animaux y compris les espèces d'élevage, les animaux de compagnie, les petits mammifères et les reptiles. Les animaux porteurs sont souvent sains en apparence ; néanmoins, les humains peuvent contracter l'infection après un contact direct ou indirect avec un animal atteint, ce qui induit un fardeau significatif associé à ces maladies. D'après les estimations, environ 14 % des 3,2 millions de cas annuels d'infections par des agents pathogènes entériques aux États-Unis d'Amérique ont pour origine un contact avec des animaux. Aux États-Unis, la surveillance des agents pathogènes entériques est basée sur la collecte et l'interprétation des résultats de laboratoire et des données épidémiologiques. Les auteurs sont néanmoins convaincus de la nécessité de recourir à une approche collaborative, multisectorielle et transdisciplinaire (en d'autres termes, une approche Une seule santé) pour la collecte et l'analyse des données, à tous les niveaux. Ils considèrent également que la surveillance des infections entériques reposera à l'avenir sur le développement de technologies avancées dans le domaine de la détection et de la caractérisation des agents pathogènes, notamment le séquençage génomique et la métagénomique. En particulier, le recours au séquençage du génome entier afin de comparer les séquences d'agents pathogènes d'origine humaine, alimentaire, animale et environnementale permettra d'anticiper l'apparition d'antibiorésistances, de déterminer le degré de parenté génétique de ces agents et d'identifier les foyers provenant d'une même source. Les auteurs décrivent trois foyers récents d'infections entériques humaines survenus dans plusieurs états des États-Unis et soulignent à quel point l'exercice d'une surveillance sanitaire intégrée a été déterminant pour la détection de ces foyers et la mise en œuvre d'une réponse appropriée. Un partage accru d'informations entre les laboratoires et les épidémiologistes de santé publique et animale aux niveaux local, national, régional et international pourrait contribuer à améliorer la surveillance des menaces émergentes pesant sur la santé animale et humaine et à mettre en œuvre de nouvelles modalités de prévention.

En el tracto intestinal de muchos animales, entre ellos ganado, mascotas, pequeños mamíferos o reptiles, puede haber patógenos intestinales como salmonelas no tifoideas, Campylobacter o Escherichia coli. A menudo los animales parecen sanos, pese a lo cual las personas pueden infectarse por contacto directo o indirecto con ellos, lo que da lugar a una considerable carga de morbilidad. Se calcula que, de los 3,2 millones de casos de enfermedad que estos patógenos intestinales causan al año en los EE. UU., un 14% es atribuible al contacto con animales. La vigilancia de patógenos intestinales que se practica en los EE. UU. incluye la compilación e interpretación de datos tanto epidemiológicos como de laboratorio. En opinión de los autores, sin embargo, es preciso que la obtención y el análisis de datos respondan a un planteamiento de colaboración multisectorial y transdisciplinar ­ esto es, a la lógica de Una sola salud ­ que abarque todos los niveles. Los autores apuntan además que el futuro de la vigilancia de las enfermedades intestinales pasa por el desarrollo de tecnologías más eficaces de detección y caracterización de patógenos, como la secuenciación genómica o la metagenómica. En particular, el uso de la secuenciación de genomas completos para comparar entre sí las secuencias genéticas de patógenos intestinales presentes en personas, alimentos, animales y el medio ambiente puede ayudar a predecir la aparición de resistencias a los antimicrobianos en estos patógenos, determinar su parentesco genético e identificar brotes vinculados con un origen común. Los autores, tras describir tres recientes brotes de enfermedad intestinal humana ligados al contacto con animales que afectaron a varios estados de los EE. UU., explican la función esencial que cumplió la vigilancia integrada de enfermedades para detectar esos brotes y responder a ellos. El intercambio de más datos entre los laboratorios de salud pública y sanidad animal y los epidemiólogos a escala local, nacional, regional e internacional puede ser de ayuda para mejorar la vigilancia de amenazas sanitarias y zoosanitarias emergentes y abrir nuevas posibilidades de prevención.

Pharmacologic evidence to support clinical decision making for peripartum methadone treatment.

RATIONALE: Limited pharmacological data are available to guide methadone treatment during pregnancy and postpartum. OBJECTIVES: Study goals were to (1) characterize changes in methadone dose across childbearing, (2) determine enantiomer-specific methadone withdrawal kinetics from steady state during late pregnancy, (3) assess enantiomer-specific changes in methadone level/dose (L/D) ratios across childbearing, and (4) explore relationships between CYP2B6, CYP2C19, and CYP3A4 single-nucleotide polymorphisms and maternal dose, plasma concentration, and L/D. METHODS: Methadone dose changes and timed plasma samples were obtained for women on methadone (n = 25) followed prospectively from third trimester of pregnancy to 3 months postpartum. RESULTS: Participants were primarily white, Medicaid insured, and multiparous. All women increased their dose from first to end of second trimester (mean peak increase = 23 mg/day); 71 % of women increased from second trimester to delivery (mean peak increase = 19 mg/day). Half took a higher dose 3 months postpartum than at delivery despite significantly larger clearance during late pregnancy. Third trimester enantiomer-specific methadone half-lives (range R-methadone 14.7-24.9 h; S-methadone, 8.02-18.9 h) were about half of those reported in non-pregnant populations. In three women with weekly 24-h methadone levels after delivery, L/D increased within 1-2 weeks after delivery. Women with the CYP2B6 Q172 variant GT genotype have consistently higher L/D values for S-methadone across both pregnancy and postpartum. CONCLUSIONS: Most women require increases in methadone dose across pregnancy. Given the shorter half-life and larger clearances during pregnancy, many pregnant women may benefit from split methadone dosing. L/D increases quickly after delivery and doses should be lowered rapidly after delivery.

Central inhibition of gonadotropin-releasing hormone secretion in the growth-restricted hypogonadotropic female sheep.

Growth retardation induced by dietary restriction results in hypogonadotropism, and thus, puberty is delayed. The present studies determined 1) whether reduced LH secretion in the growth-retarded condition is due to a reduction in the frequency and/or in the amplitude of GnRH secretion, and 2) whether the mechanism regulating LH secretion is being actively inhibited via central mechanisms. To determine whether GnRH pulse frequency and/or amplitude are reduced during growth restriction, blood samples were simultaneously collected from pituitary portal blood for GnRH and from jugular blood for LH determinations over a 4-h period in ovariectomized lambs (52 wk of age) that were either growth restricted (28 kg; n = 8) or growing normally (60 kg; n = 7). As expected, the growth-restricted females were hypogonadotropic and exhibited a long LH interpulse interval compared with the normally growing females. However, although the GnRH interpulse interval was longer in the growth-restricted lambs compared with that in the normally growing lambs, the pattern of GnRH secretion did not directly correspond with that of LH secretion in the growth-restricted group. In addition, high amplitude GnRH pulses that coincided with LH pulses and small, low amplitude GnRH pulses without a concomitant LH pulse occurred. The second study tested the hypothesis that diet-induced hypogonadotropism is the result of actively inhibited central mechanisms by investigating the effects of the nonspecific central nervous system inhibitor, sodium pentobarbital, on pulsatile LH secretion in the growth-restricted lamb. Serial blood samples were collected from 11 ovariectomized lambs that were maintained at weaning weight (approximately 20 kg) by reduced diet. After a 4-h pretreatment period, six of the lambs were anesthetized with sodium pentobarbital for 4 h; the other five lambs were untreated and served as controls. Pentobarbital anesthesia reduced the LH interpulse interval (increased the frequency) and increased mean LH levels. These findings suggest that during growth restriction hypogonadotropism arises from a central inhibition of GnRH neurons and is manifest as a decrease in both frequency and amplitude of GnRH pulses.

An outbreak of salmonellosis among children attending a reptile exhibit at a zoo.

OBJECTIVE: In January 1996, an outbreak of diarrhea caused by Salmonella Enteritidis occurred in children attending a Komodo dragon exhibit at a metropolitan zoo. We sought to determine the extent of the outbreak and mode of transmission. STUDY DESIGN: A case-control study was conducted. Controls were randomly selected from zoo membership lists and matched to patients by age group and date of exhibit visit. RESULTS: Of 65 patients identified, 39 had confirmed and 26 had suspected cases. The median age was 7 years (range, 3 months to 48 years); 55% were enrolled in the case-control study. No patients and two (4%) controls reported touching a dragon; however, 83% of patients but only 52% of controls touched the wooden barrier that surrounded the dragon pen (odds ratio = 4.0, 95% CI 1.2 to 13.9). Washing hands at the zoo after visiting the dragons was highly protective (OR = 0.14, 95% CI 0.03 to 0.7). Cultures from the patients, one dragon, and the exhibit barriers yielded Salmonella Enteritidis, phage type 8. On the basis of an attack rate of 4.3% among exhibit attendees under 13 years old on whom data were collected, we estimate that 315 additional cases of salmonellosis occurred among visitors in this age group. CONCLUSION: This large outbreak demonstrates the importance of environmental contamination in the transmission of Salmonella from reptiles, and the protective value of hand washing. Recommendations regarding reptile exhibits and reptilian pets should emphasize this indirect route.

Widespread dissemination of a drug-susceptible strain of Mycobacterium tuberculosis.

In New York City, a large proportion of new tuberculosis cases has been caused by 1 drug-susceptible strain (called C strain) of Mycobacterium tuberculosis. Between 1991 and 1994, among >600 tuberculosis patients consecutively identified in four large hospitals in the city, 54 with C strain, 69 with non-C cluster pattern strains, and 42 with noncluster pattern strains were studied. Susceptibility to reactive nitrogen intermediates (RNI) of selected isolates was compared. In a case-control analysis, 51% of patients with C strain, 28% with non-C cluster strains (P < .05), and 14% with noncluster strains (P < .01) were found to be injection drug users. C strain but not 13 other unrelated isolates were resistant to RNI. Injection drug use may provide a selective pressure for an RNI-resistant tubercle bacillus to emerge, which may give the organism a biologic advantage and explain the widespread dissemination of C strain M. tuberculosis within the city.

Risk factors and outcome of human immunodeficiency virus-infected patients with sporadic multidrug-resistant tuberculosis in New York City.

SETTING: An 880 bed university teaching hospital in New York City. OBJECTIVE: To assess risk factors and outcome for sporadic cases of multidrug-resistant tuberculosis (MDR-TB) in persons with human immunodeficiency virus (HIV) infection. DESIGN: In a retrospective cohort analysis, 13 HIV-positive patients with MDR-TB (cases) diagnosed between January 1991 and December 1993 were compared to 31 HIV-infected patients with susceptible or single drug-resistant tuberculosis (controls) diagnosed during the same time period to assess for differences in risk factors and outcome. RESULTS: Risk factors for MDR-TB included homosexual contact as a risk for HIV transmission, prior antiretroviral therapy and Pneumocystis carinii prophylaxis. Fatality rates were 62% for MDR-TB patients and 26% for controls (P < 0.04). The median survival time was 5.8 months for cases and 9.8 months for controls. Risk factors associated with death included multidrug-resistance and CD4-lymphocyte counts below 200. CONCLUSION: Sporadic MDR-TB infection in HIV-infected patients is associated with increased morbidity and mortality compared to infection with susceptible or single-drug-resistant TB. The median survival for HIV-infected patients with MDR-TB in this study is, however, two to three times longer than previously reported in MDR-TB outbreaks.

Factors affecting credibility in a simulated sexual harassment hearing.

PIP: This paper presents two studies investigating judgments in a simulated sexual harassment hearing in which 240 male and female undergraduates participated. The transcript presented a female student's allegations of sexual harassment against a male professor. In the first experiment, 4 versions of a transcript were created, varying the aggressiveness of the attack on the female student complainant and the status of the accused professor. The findings supported the hypothesis that an aggressive attack negatively affects believability of the victim. The findings are also consistent with previous studies, which found out that denial was an effective technique for handling attacks. In the second experiment, the case was modified as to the emotionality of both the victim and the accused and the time of the between the occurrence and the reporting of the alleged harassment incident (1 month vs. 6 months). The results indicated that emotionality was important to decisions about the severity of punishment and guilt; when the victim was emotional, the defendant was punished more severely. Both experiments indicated that process variables (e.g., aggressiveness of attack) might be important in the perception of sexual harassment.^ieng

Tuberculosis among urban health care workers: a study using restriction fragment length polymorphism typing.

Cases of tuberculosis identified during 1992-1994 through an active tuberculosis surveillance network among six hospitals that serve New York City (the TBNetwork) were analyzed according to the occupational status of the patients. Clinical data were obtained by review of medical records, and restriction fragment length polymorphism (RFLP) typing of Mycobacterium tuberculosis isolates was performed. No known nosocomial outbreaks of tuberculosis occurred at these hospitals in the study period. Occupational status was known for 142 of 201 patients whose isolates were available for strain typing. Patients infected by organisms with a clustered strain typing pattern, as determined by RFLP analysis, were presumed to have recently acquired disease. RFLP typing revealed that isolates from 13 (65%) of 20 health care workers and 50 (41%) of 122 non-health care workers had a clustered RFLP pattern. The strains infecting eight (89%) of nine health care workers seropositive for human immunodeficiency virus (HIV) had a clustered RFLP pattern. Multivariate analysis of 75 patients with known HIV and occupational status revealed that HIV status (P = .03) and health care worker status (P = .02; RR = 2.77) were independent risk factors for a clustered RFLP strain. These findings suggest that many of the apparently sporadic cases of tuberculosis among health care workers may be due to unrecognized occupational transmission.

Transmission of multidrug-resistant tuberculosis in a large urban setting.

Multidrug resistance has become an increasingly important problem in the control and prevention of tuberculosis in large urban centers. Although several small outbreaks of multidrug-resistant (MDR) tuberculosis in New York City have been reported, the increase in the number of cases is not fully explained by these recognized outbreaks, and the modes of transmission have not been clearly delineated. Transmission patterns of MDR tuberculosis in New York City, therefore, were studied by stratifying Mycobacterium tuberculosis isolates from 167 newly diagnosed tuberculosis patients according to their DNA restriction fragment length polymorphisms (RFLP). Forty-three (34%) of 127 drug-susceptible isolates and 19 (79%) of 24 multidrug-resistant isolates had RFLP patterns representing possible recent exogenous infection (primary tuberculosis). Patients who had such isolates were more likely to be seropositive for human immunodeficiency virus (58%; p < 0.05), non-Hispanic black (56%; p < 0.005), U.S.-born (57%; p < 0.001), and have MDR tuberculosis (79%; p < 0.0005). In a logistic regression model, primary tuberculosis remained significantly associated with MDR tuberculosis and black race. In contrast to previous reports, in New York City recent exogenous transmission accounts for most new cases of multidrug-resistant tuberculosis.

Double-repetitive-element PCR method for subtyping Mycobacterium tuberculosis clinical isolates.

We describe a rapid method for subtyping Mycobacterium tuberculosis based on PCR amplification of segments located between two distinct DNA repetitive elements. This method, double-repetitive-element PCR, classified 46 clinical isolates as having 25 distinct patterns; the conventional restriction fragment length polymorphism analysis classified the same isolates as having 23 distinct patterns. The double-repetitive-element PCR is a rapid subtyping method that has a discriminating power similar to that of the restriction fragment length polymorphism method.