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In February 2020, during the early days of the COVID-19 pandemic, 232 evacuees from Wuhan, China, were placed under federal 14-day quarantine upon arrival at a US military base in San Diego, California. We describe the monitoring of evacuees and responders for symptoms of COVID-19, case and contact investigations, infection control procedures, and lessons learned to inform future quarantine protocols for evacuated people from a hot spot resulting from a novel pathogen. Thirteen (5.6%) evacuees had COVID-19-compatible symptoms and 2 (0.9%) had laboratory-confirmed SARS-CoV-2. Two case investigations identified 43 contacts; 3 (7.0%) contacts had symptoms but tested negative for SARS-CoV-2 infection. Daily symptom and temperature screening of evacuees and enacted infection control procedures resulted in rapid case identification and isolation and no detected secondary transmission among evacuees or responders. Lessons learned highlight the challenges associated with public health response to a novel pathogen and the evolution of mitigation strategies as knowledge of the pathogen evolves.

To determine prevalence of, seroprevalence of, and potential exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among a cohort of evacuees returning to the United States from Wuhan, China, in January 2020, we conducted a cross-sectional study of quarantined evacuees from 1 repatriation flight. Overall, 193 of 195 evacuees completed exposure surveys and submitted upper respiratory or serum specimens or both at arrival in the United States. Nearly all evacuees had taken preventive measures to limit potential exposure while in Wuhan, and none had detectable SARS-CoV-2 in upper respiratory tract specimens, suggesting the absence of asymptomatic respiratory shedding among this group at the time of testing. Evidence of antibodies to SARS-CoV-2 was detected in 1 evacuee, who reported experiencing no symptoms or high-risk exposures in the previous 2 months. These findings demonstrated that this group of evacuees posed a low risk of introducing SARS-CoV-2 to the United States.

During early embryogenesis, the vertebrate embryo extends from anterior to posterior because of the progressive addition of cells from a posteriorly localized neuromesodermal progenitor (NMp) population. An autoregulatory loop between Wnt and Brachyury/Tbxt is required for NMps to retain mesodermal potential and, hence, normal axis development. We recently showed that Hox13 genes help to support body axis formation and to maintain the autoregulatory loop, although the direct Hox13 target genes were unknown. Here, using a new method for identifying in vivo transcription factor-binding sites, we identified more than 500 potential Hox13 target genes in zebrafish. Importantly, we found two highly conserved Hox13-binding elements far from the tbxta transcription start site that also contain a conserved Tcf7/Lef1 (Wnt response) site. We show that the proximal of the two elements is sufficient to confer somitogenesis-stage expression to a tbxta promoter that, on its own, only drives NMp expression during gastrulation. Importantly, elimination of this proximal element produces shortened embryos due to aberrant formation of the most posterior somites. Our study provides a potential direct connection between Hox13 and regulation of the Wnt/Brachyury loop.

Although canonical autophagy regulation requires a multi-protein complex centered on the Ser/Thr-kinase Atg1 (mammalian Ulk1/2), alternative signals can induce autophagy independent of Atg1 through unknown mechanisms. Here we identify the Drosophila Ulk3 ortholog, another Drosophila Unc-51-like kinase (ADUK), as an Atg1-independent autophagy inducer. ADUK interacts with Atg1 complex members Atg13 and 200 kDa FAK family kinase-interacting protein, and requires Atg13 but not Atg1 for autophagy induction. Loss of ADUK shortens adult lifespan and reduces the autophagic response to a chemical stressor, dimethyl sulfoxide. However, ADUK is not required for autophagy induction by Atg1-dependent nutrient or developmental cues. Atg1 and ADUK/Ulk3 thus represent alternative catalytic components of a shared autophagy kinase complex.

An essential element of Ebola control involves monitoring and movement restrictions for people who come into contact with an Ebola patient while the patient is infectious. Although procedures can vary by local regulations, monitoring and movement restrictions for Ebola contacts normally last for 21 days after the last exposure to the infectious patient. Contact monitoring and movement restrictions allow for early identification of disease to prevent further transmission. However, movement restrictions also limit a contact’s ability to meet some of his or her own daily living needs. Ensuring that measures and processes are in place to provide for these needs is an important component of implementing movement restrictions. Stigmatization of contacts because of community fears creates an additional need for supports. A previous report of a related Ebola investigation in Texas described the needs of Ebola contacts, including basic needs for food, financial assistance, and education. In that investigation, health officials found that meeting the needs of Ebola contacts was essential to successful contact monitoring. Providing for the daily needs of people whose movement is restricted during an outbreak response is not new to public health. This need was noted during the typhus and cholera epidemics in New York City in 1892 and during the severe acute respiratory syndrome epidemic in Taiwan and Canada in 2013, where affected individuals experienced uncomfortable surroundings, discrimination, uncertainty, and a need for family support. We discuss the importance of preparing for such daily needs and how the Ebola experience in Ohio adds to the Texas report to inform future situations in which movement restrictions are needed. The Ebola Experience in Ohio

Each year, >9 million foodborne illnesses are estimated to be caused by major pathogens acquired in the United States. Preventing these illnesses is challenging because resources are limited and linking individual illnesses to a particular food is rarely possible except during an outbreak. We developed a method of attributing illnesses to food commodities that uses data from outbreaks associated with both simple and complex foods. Using data from outbreak-associated illnesses for 1998–2008, we estimated annual US foodborne illnesses, hospitalizations, and deaths attributable to each of 17 food commodities. We attributed 46% of illnesses to produce and found that more deaths were attributed to poultry than to any other commodity. To the extent that these estimates reflect the commodities causing all foodborne ill ness, they indicate that efforts are particularly needed to prevent contamination of produce and poultry. Methods to incorporate data from other sources are needed to improve attribution estimates for some commodities and agents.

Clostridium difficile, the most commonly recognized diarrheagenic pathogen among hospitalized persons, can cause outpatient diarrhea. Of 1,091 outpatients with diarrhea, we found 43 (3.9%) who were positive for C. difficile toxin. Only 7 had no recognized risk factors, and 3 had neither risk factors nor co-infection with another enteric pathogen.

Premarket standardized testing for Acanthamoeba spp. is warranted., An outbreak of Acanthamoeba keratitis, a rare, potentially blinding, corneal infection, was detected in the United States in 2007; cases had been increasing since 2004. A case–control study was conducted to investigate the outbreak. We interviewed 105 case-patients from 30 states and 184 controls matched geographically and by contact lens use. Available contact lenses, cases, solutions, and corneal specimens from case-patients were cultured and tested by molecular methods. In multivariate analyses, case-patients had significantly greater odds of having used Advanced Medical Optics Complete Moisture Plus (AMOCMP) solution (odds ratio 16.9, 95% confidence interval 4.8–59.5). AMOCMP manufacturing lot information was available for 22 case-patients, but none of the lots were identical. Three unopened bottles of AMOCMP tested negative for Acanthamoeba spp. Our findings suggest that the solution was not intrinsically contaminated and that its anti-Acanthamoeba efficacy was insufficient. Premarket standardized testing of contact lens solutions for activity against Acanthamoeba spp. is warranted.

Degradation of cellular material by autophagy is essential for cell survival and homeostasis, and requires intracellular transport of autophagosomes to encounter acidic lysosomes through unknown mechanisms. Here we identify the PX domain-containing kinesin Klp98A as a novel regulator of autophagosome formation, transport and maturation in Drosophila. Depletion of Klp98A caused abnormal clustering of autophagosomes and lysosomes at the cell center and reduced the formation of starvation-induced autophagic vesicles. Reciprocally, overexpression of Klp98A redistributed autophagic vesicles toward the cell periphery. These effects were accompanied by reduced autophagosome-lysosome fusion and autophagic degradation. In contrast, depletion of the conventional kinesin heavy chain caused a similar mislocalization of autophagosomes without perturbing their fusion with lysosomes, indicating that vesicle fusion and localization are separable, independent events. Klp98A-mediated fusion required the endolysosomal GTPase Rab14, which interacted and colocalized with Klp98A and required Klp98A for normal localization. Thus, Klp98A coordinates the movement and fusion of autophagic vesicles by regulating their positioning and interaction with the endolysosomal compartment.

BACKGROUND An estimated 1.4 million salmonella infections occur annually in the United States. The majority of these infections are foodborne, but many are acquired by contact with animals. In August 2004, isolates of Salmonella enterica serotype Typhimurium, which were indistinguishable from one another by pulsed-field gel electrophoresis (PFGE), were obtained from eight hamsters from a Minnesota pet distributor. We conducted an investigation to determine whether human cases of salmonella could be linked to this rodent-borne strain. METHODS To identify cases of human infection with S. enterica serotype Typhimurium potentially related to pet rodents, we reviewed salmonella PFGE patterns submitted to the National Molecular Subtyping Network for Foodborne Disease Surveillance. Patients with isolates matching the hamster strain were interviewed about exposure to pet rodents. Implicated rodents were traced to pet stores, distributors, and breeders. RESULTS We identified matching S. enterica serotype Typhimurium isolates from 28 patients in whom the onset of illness occurred between December 2003 and September 2004. Of 22 patients (or in the case of children, their parents) interviewed, 13 patients (59%) in 10 states reported exposure to pet hamsters, mice, or rats, and 2 (9%) had secondary infections. The median age of the 15 patients with primary or secondary rodent exposure was 16 years, and 6 patients (40%) were hospitalized. Thirteen associated pet stores supplied by seven distributors were identified in 10 states. No single source of the rodents was identified. The outbreak strain of S. enterica serotype Typhimurium was cultured from a patient's pet mouse and from seven hamsters from pet stores. Closely related S. enterica serotype Typhimurium isolates were cultured from rodent cages and reusable transport containers at a pet distributor. Human, rodent, and environmental isolates were resistant to ampicillin, chloramphenicol, streptomycin, sulfisoxazole, and tetracycline. CONCLUSIONS Pet rodents probably are an underrecognized source of human salmonella infection.

Background. Diarrhea remains a common complaint among US patients who seek medical attention. Methods. We performed a prospective study to determine the etiology of diarrheal illness among patients and control subjects of all ages presenting to the emergency departments and outpatient clinics of 2 large academic hospitals in Baltimore, Maryland, and New Haven, Connecticut. We used molecular methods to detect the presence of diarrheagenic Escherichia coli pathotypes, including enteroaggregative E. coli (EAEC), as well as Shiga toxin-producing, cytodetaching, enterotoxigenic and enteropathogenic E. coli. Results. Of the pathotypes sought, only EAEC was found in an appreciable proportion (4.5%) of case patients, and it was found more frequently among case patients than control subjects (P

Enterobacter sakazakii kills 40%–80% of infected infants and has been associated with powdered formula. We analyzed 46 cases of invasive infant E. sakazakii infection to define risk factors and guide prevention and treatment. Twelve infants had bacteremia, 33 had meningitis, and 1 had a urinary tract infection. Compared with infants with isolated bacteremia, infants with meningitis had greater birthweight (2,454 g vs. 850 g, p = 0.002) and gestational age (37 weeks vs. 27.8 weeks, p = 0.02), and infection developed at a younger age (6 days vs. 35 days, p

Escherichia coli O157 infections cause an estimated 60 deaths and 73000 illnesses annually in the United States. A marked summer peak in incidence is largely unexplained. We investigated an outbreak of E. coli O157 infections at an agricultural fair in Ohio and implicated consumption of beverages made with fairground water and sold by a geographically localized group of vendors who were all on the same branch of the fairground water distribution system. To examine county fair attendance as a risk factor for infection, we conducted two further epidemiological studies. In the first, we enhanced surveillance for E. coli O157 infections in 15 Northeast Ohio counties during the 2000 agricultural fair season and showed increased risk of E. coli O157 infection among fair attendees. In the second study, we examined Ohio Public Health Laboratory Information Service (PHLIS) data for 1999 using a time-varying covariate proportional hazards model and demonstrated an association between agricultural fairs and E. coli O157 infections, by county. Agricultural fair attendance is a risk factor for E. coli O157 infection in the United States and may contribute to the summer peak in incidence. Measures are needed to reduce transmission of enteric pathogens at agricultural fairs.

We estimated direct medical and nonmedical costs associated with a false diagnosis of tuberculosis (TB) caused by laboratory cross-contamination of Mycobacterium tuberculosis cultures in Massachusetts in 1998 and 1999. For three patients who received misdiagnoses of active TB disease on the basis of laboratory cross-contamination, the costs totaled U.S. dollars 32618. Of the total, 97% was attributed to the public sector (local and state health departments, public health hospital and laboratory, and county and state correctional facilities); 3% to the private sector (physicians, hospitals, and laboratories); and1% to the patient. Hospitalizations and inpatient tests, procedures, and TB medications accounted for 69% of costs, and outpatient TB medications accounted for 18%. The average cost per patient was dollars 10873 (range, dollars 1033-dollars 21306). Reducing laboratory cross-contamination and quickly identifying patients with cross-contaminated cultures can prevent unnecessary and potentially dangerous treatment regimens and anguish for the patient and financial burden to the health-care system.

The National Tuberculosis Genotyping and Surveillance Network was established in 1996 to perform a 5-year, prospective study of the usefulness of genotyping Mycobacterium tuberculosis isolates to tuberculosis control programs. Seven sentinel sites identified all new cases of tuberculosis, collected information on patients and contacts, and obtained patient isolates. Seven genotyping laboratories performed DNA fingerprinting analysis by the international standard IS6110 method. BioImage Whole Band Analyzer software was used to analyze patterns, and distinct patterns were assigned unique designations. Isolates with six or fewer bands on IS6110 patterns were also spoligotyped. Patient data and genotyping designations were entered in a relational database and merged with selected variables from the national surveillance database. In two related databases, we compiled the results of routine contact investigations and the results of investigations of the relationships of patients who had isolates with matching genotypes. We describe the methods used in the study.

Quality assessment exercises were conducted to evaluate the reproducibility of IS6110 DNA fingerprinting performed by eight laboratories in the National Tuberculosis Genotyping and Surveillance Network. Three panels, each with 8 to 16 isolates, were typed at all laboratories, resulting in 280 images. When the pattern obtained by the majority for each isolate was used as the standard, exact matches were obtained for 73% of patterns; 90% and 97% of patterns matched within one- and two-band differences, respectively. A second approach involved retyping of randomly selected isolates at the Centers for Disease Control and Prevention. Retyping was done for 8–19 isolates per laboratory (76 total). Paired images matched exactly for 54% of isolates and within one and two band differences, 78% and 93%, respectively. We evaluated reasons for mismatching. We also evaluated the reproducibility of spoligotyping using a test panel of 13 isolates; a discrepancy of 1 in 91 results was noted.

DNA fingerprinting was used to evaluate epidemiologically linked case pairs found during routine tuberculosis (TB) contact investigations in seven sentinel sites from 1996 to 2000. Transmission was confirmed when the DNA fingerprints of source and secondary cases matched. Of 538 case pairs identified, 156 (29%) did not have matching fingerprints. Case pairs from the same household were no more likely to have confirmed transmission than those linked elsewhere. Case pairs with unconfirmed transmission were more likely to include a smear-negative source case (odds ratio [OR] 2.0) or a foreign-born secondary case (OR 3.4) and less likely to include a secondary case

DNA fingerprinting of Mycobacterium tuberculosis--a relatively new laboratory technique--offers promise as a powerful aid in the prevention and control of tuberculosis (TB). Established in 1996 by the Centers for Disease Control and Prevention (CDC), the National Tuberculosis Genotyping and Surveillance Network was a 5-year prospective, population-based study of DNA fingerprinting conducted from 1996 to 2000. The data from this study suggest multiple molecular epidemiologic and program management uses for DNA fingerprinting in TB public health practice. From these data, we also gain a clearer understanding of the overall diversity of M. tuberculosis strains as well as the presence of endemic strains in the United States. We summarize the key findings and the impact that DNA fingerprinting may have on future approaches to TB control. Although challenges and limitations to the use of DNA fingerprinting exist, the widespread implementation of the technique into routine TB prevention and control practices appears scientifically justified.

The epidemiology of E. sakazakii is poorly understood, because infection is rare and is not a reportable condition in most countries. However, incidence appears to differ by demographic group and underlying health status; infants and immunocompromised persons appear to be at higher risk of invasive infections than other persons. Among four reported adult cases of bacteremia, two had surgical procedures with complications shortly before infection, and one of these patients died despite treatment with appropriate antimicrobial agents. Another adult developed urosepsis secondary to urinary retention, and a fourth developed sepsis without an obvious source; both of these patients were treated with appropriate antimicrobial agents and survived. Standard blood, cerebrospinal fluid (CSF), urine, and tissue culture specimens can be used to diagnose E. sakazakii infection, and isolates grow well on standard nonselective media. There are no comparative studies guiding treatment options for E. sakazakii infections. However, inference from antimicrobial susceptibility studies may be useful. Thus, investigations of outbreaks have provided the most information about the epidemiology of E. sakazakii infections. A section also reviews published investigations of outbreaks of E. sakazakii disease.

The term autophagy refers to the engulfment and degradation of cytoplasmic components within the lysosome. This process can benefit cells and organisms by removing damaged, superfluous, or harmful cellular components, and by generating a supply of recycled macromolecules that can support biosynthesis or energy production. Recent interest in autophagy has been driven by its potential role in several disease-related phenomena including neurodegeneration, cancer, immunity and aging. Drosophila provides a valuable animal model context for these studies, and work in this system has also begun to identify novel developmental and physiological roles of autophagy. Here, we provide an overview of methods for monitoring autophagy in Drosophila, with a special emphasis on the larval fat body. These methods can be used to investigate whether observed vesicles are of autophagic origin, to determine a relative rate of autophagic degradation, and to identify specific step(s) in the autophagic process in which a given gene functions.

Epidemiologic relatedness of Mycobacterium tuberculosis isolates from Arkansas residents diagnosed with tuberculosis in 1992-1993 was assessed using IS6110- and pTBN12-based restriction fragment length polymorphism (RFLP) and epidemiologic investigation. Patients with isolates having similar IS6110 patterns had medical records reviewed and were interviewed to identify epidemiologic links. Complete RFLP analyses were obtained for isolates of 235 patients; 78 (33%) matched the pattern of > or = 1 other isolate, forming 24 clusters. Epidemiologic connections were found for 33 (42%) of 78 patients in 11 clusters. Transmission of M. tuberculosis likely occurred many years in the past for 5 patients in 2 clusters. Of clusters based only on IS6110 analyses, those with > or = 6 IS6110 copies had both a significantly greater proportion of isolates that matched by pTBN12 analysis and patients with epidemiologic connections, indicating IS6110 patterns with few bands lack strain specificity. Secondary RFLP analysis increased specificity, but most clustered patients still did not appear to be epidemiologically related. RFLP clustering in rural areas may not represent recent transmission.

After a dramatic increase in the incidence of TB in the United States from 1985 to 1992, the epidemiology of TB changed, with both the number of cases and the incidence of TB decreasing since 1992. The decreases have been focal, however, affecting only certain geographic areas (e.g., New York, California, and New Jersey) and certain populations (e.g., 25-44 year age group and people born in the United States). The factors responsible for the decrease in those areas and populations are multiple but the most important are thought to be improvements in TB control and treatment programs in communities serving populations at greatest risk for TB. Despite the overall decline in TB cases, the numbers of foreign-born people with TB continue to increase. Factors contributing to the increase in TB among foreign-born people include the prevalence of TB in the country of origin, duration of residence in the United States after immigration, inadequate screening for or treatment of TB before entering the United States, and inadequate follow-up of those who have entered the United States with noninfectious TB (i.e., abnormal chest radiograph with negative sputum smears). Control of TB among the foreign-born population is essential if the current downward trend in reported TB cases in the United States is to be maintained. The HIV epidemic had a significant impact on the increase in TB incidence in the United States in the late 1980s but improvements in measures to control transmission of TB appear to have been effective in reversing that trend. The current national decrease trend in TB morbidity can be sustained through organized efforts by federal and private agencies and state and local health departments to ensure that all people with TB are identified and treated promptly. Such efforts must be aimed at areas and populations identified as high risk for TB, especially foreign-born people and people who are infected with HIV.

New foodborne pathogens continue to emerge, and the globalization of the food supply means that the safety of our food depends on policies and practices in many countries. Public health surveillance of foodborne bacterial pathogens depends on culture, isolation, and subtyping. New diagnostic strategies that bypass culture threaten public health surveillance in the short-term but offer the potential for more refined and rapid outbreak detection in the future. Infectious disease clinicians play a critical role in diagnosis and reporting because they may be the first to suspect a new problem and often link clinical and public health communities.

Ten years have elapsed since the World Health Organization issued its first global alert for an unexplained illness named severe acute respiratory syndrome (SARS). The anniversary provides an opportunity to reflect on the international response to this new global microbial threat. While global surveillance and response capacity for public health threats have been strengthened, critical gaps remain. Of 194 World Health Organization member states that signed on to the International Health Regulations (2005)

A search for the source of infection for four children with tuberculosis (TB) identified a university student with cavitary and laryngeal TB. An investigation was conducted at the university, including tuberculin skin test (TST) screening and the use of questionnaires, chest radiographs, and DNA fingerprint analyses of Mycobacterium tuberculosis isolates. Six students with active TB were identified. All were linked to the source case. TSTs were positive for 22.4% of 419 students who had contact with the source case vs. 3.6% of 1,306 students without contact. The odds of a positive TST increased to 9.0 with 80 hours of classroom contact. Infectiousness increased significantly in the last of three semesters during which the source case was symptomatic (RR of a positive TST in classmates, 4.8; 95% CI, 1.8-11.8). TST conversions were documented in 23 students; eight had, at most, 5 hours of classroom contact. The source case was highly infectious; transmission following only a few hours of exposure was documented. Her infectiousness increased as her clinical course progressed. This report illustrates the potential infectiousness of TB cases and demonstrates important aspects of tuberculosis control.

Public health surveillance is essential to the practice of public health and to guide prevention and control activities and evaluate outcomes of such activities. With advances in information sciences and technology, changes in methodology, data availability and data synthesis, and expanded health information needs, the question arises whether redefining public health surveillance is needed for the 21st century. The current definition is "Public health surveillance is the ongoing, systematic collection, analysis, and interpretation of health data, essential to the planning, implementation and evaluation of public health practice, closely integrated with the dissemination of these data to those who need to know and linked to prevention and control."

To better understand the sources of foodborne illness, we propose a scheme for categorizing foods implicated in investigations of outbreaks of foodborne diseases. Because nearly 2000 foods have been reported as causing outbreaks in the United States, foods must be grouped for meaningful analyses.We defined a hierarchy of 17 mutually exclusive food commodities. We defined the following three commodity groups from which nearly all food is derived: aquatic animals, land animals, and plants. We defined three commodities in aquatic animals, six in land animals, and eight in plants. We considered each food as a set of ingredients composed of one or more commodities. We defined a simple food as one made of ingredients that are all in one commodity and a complex food as one containing ingredients in more than one commodity. We determined likely ingredients using a panel of epidemiologists and a web-based search process.We assigned 1709 (95%) of the 1794 foods implicated in outbreaks of foodborne diseases reported to Centers for Disease Control and Prevention from 1973 to 2006. Of those, 987 (57%) were simple foods and 722 (43%) were complex foods.This categorization may serve as an input for modeling the attribution of human illness to specific food commodities and could be used by policy makers, health officials, regulatory agencies, and consumer groups to evaluate the contribution of various food commodities to illness.

Background. Infection due to Salmonella species causes an estimated 1.4 million illnesses and 400 deaths annually in the United States. Orange juice is a known vehicle of salmonellosis, for which regulatory controls have recently been implemented. We investigated a nationwide outbreak of Salmonella infection to determine the magnitude of the outbreak and to identify risk factors for infection. Methods. We identified cases through national laboratory-based surveillance. In a case-control study, we defined a case as infection with Salmonella serotype Typhimurium that demonstrated the outbreak pulsed-field gel electrophoresis pattern in a person with illness onset from 1 May through 31 July 2005; control subjects were identified through random digit dialing. Results. We identified 152 cases in 23 states. Detailed information was available for 95 cases. The median age of patients was 23 years; 46 (48%) of the 95 patients were female. For 38 patients and 53 age-group matched control subjects in 5 states, illness was associated with consuming orange juice (90% vs. 43%; odds ratio, 22.2; 95% confidence interval, 3.5-927.5). In a conditional logistic regression model, illness was associated with consuming unpasteurized orange juice from company X (53% vs. 0%; odds ratio, 38.0; 95% confidence interval, 6.5 infinity). The US Food and Drug Administration found that company X was noncompliant with the juice Hazard Analysis and Critical Control Point regulation and isolated Salmonella serotype Saintpaul from company X's orange juice. Conclusions. Unpasteurized orange juice from company X was the vehicle of a widespread outbreak of salmonellosis. Although the route of contamination is unknown, noncompliance with the juice Hazard Analysis and Critical Control Point regulation likely contributed to this outbreak. Pasteurization or other reliable treatment of orange juice could prevent similar outbreaks.

We utilized denaturing gradient gel electrophoresis profiling to survey stool microbiota in 175 persons with diarrhea and 113 asymptomatic persons in a diarrhea surveillance study. Compared with healthy controls, the microbiota profiles in diarrhea cases more frequently exhibited decreased diversity and strong bands indicating the overgrowth of selected bacteria or bacterial groups.

The extent to which antibiotic-resistant bacteria are excreted by humans who have not been exposed to antibiotics is not known. Children, who rarely receive fluoroquinolones, provide opportunities to assess the frequency of fecal excretion by fluoroquinolone-naïve hosts of fluoroquinolone-resistant gram-negative bacilli. Fresh nondiarrheal stools from children were processed by screening them on agar containing ciprofloxacin to recover ciprofloxacin-resistant gram-negative bacilli. Resistant isolates were identified, and ciprofloxacin MICs were determined. Resistant Escherichia coli isolates were also analyzed for urovirulence-associated loci. Thirteen (2.9%) of 455 stools yielded ciprofloxacin-resistant E. coli (seven children), Stenotrophomonas maltophilia (four children), and Achromobacter xylosoxidans and Enterobacter aerogenes (one child each). Neither the subjects themselves nor members of their households used fluoroquinolones in the 4 weeks preceding collection. Six of the seven resistant E. coli isolates belonged to phylogenetic groups B2 and D, in which extraintestinal pathogenic E. coli bacteria are frequently found. All resistant E. coli isolates contained at least three putative E. coli virulence loci. Most ciprofloxacin-resistant bacteria were resistant to additional antibiotics. Potentially pathogenic bacteria that are resistant to therapeutically important antimicrobial agents are excreted by some humans, despite these persons' lack of exposure to the particular drugs. The sources of these resistant organisms are unknown. This underrecognized reservoir of drug-resistant potential pathogens poses public health challenges.

Background We evaluated the frequency of recovery of pathogens from children with diarrhea who presented to a pediatric emergency department and characterized the associated illnesses, to develop guidelines for performing a bacterial enteric culture. Methods We conducted a prospective cohort study of all patients with diarrhea who presented to a large regional pediatric emergency department during the period from November 1998 through October 2001. A thorough microbiologic evaluation was performed on stool specimens, and the findings were correlated with case, physician, and laboratory data. Results A total of 1626 stool specimens were studied to detect diarrheagenic bacteria and, if there was a sufficient amount of stool, Clostridium difficile toxin (688 specimens), parasites (656 specimens), and viruses (417 specimens). One hundred seventy-six (47%) of 372 specimens that underwent complete testing yielded a bacterial pathogen (Shiga toxin-producing Escherichia coli, 39 specimens [of which 28 were serotype O157:H7]; Salmonella species, 39; Campylobacter species, 25; Shigella species, 14; and Yersinia enterocolitica, 2), a viral pathogen (rotavirus, 85 specimens; astrovirus, 27; adenovirus, 18; or rotavirus and astrovirus, 8), a diarrheagenic parasite (5 specimens); or C. difficile toxin (46 specimens). Samples from 2 patients yielded both bacterial and viral pathogens. A model to identify predictors of bacterial infection found that international travel, fever, and the passing of >10 stools in the prior 24 h were associated with the presence of a bacterial pathogen. Physician judgment regarding the need to perform a stool culture was almost as accurate as the model in predicting bacterial pathogens. Conclusions Nearly one-half of the patients who presented to the emergency department with diarrhea had a definite or plausible pathogen in their stool specimens. We were unable to develop a model that was substantially better than physician judgment in identifying patients for whom bacterial culture would yield positive results. The unexpectedly high rate of C. difficile toxin warrants further examination.

Background: The frequency with which bacteria cause diarrhea evaluated in ambulatory settings is often unknown. We attempted to determine the microbiologic etiology of diarrhea in a private pediatric practice (site A) and a clinic serving largely immigrant children (site B) and to establish guidelines for bacterial culture. Methods: Children with diarrhea were prospectively enrolled, and their stools were examined for diarrheagenic bacteria, viruses and parasites. Results: A total of 123 and 103 children were enrolled at sites A and B, respectively. Stools from all (100%), 126 (55.8%), 104 (46.0%) and 75 (33.2%) were tested for bacterial enteric pathogens, parasites, Clostridium difficile toxin and viruses, respectively. Of the 75 patients whose stool underwent complete testing, 36 (48%) contained at least 1 definitive or plausible pathogen. Twelve stools (5.3%) tested positive for bacteria Campylobacter jejuni (n 7), Yersinia enterocolitica, Shigella flexneri, Shigella sonnei, Salmonella serogroup D and Salmonella Braenderup (n 1 each). One contained Blastocystis hominis, 8 contained C. difficile toxin and 16 contained viruses (9 rotavirus, 5 adenovirus and 2 astrovirus). Visible fecal blood (P 0.029), increased stool frequency (P 0.035), abdominal tenderness (P 0.011) and fecal white (P 0.001) or red blood cells (P 0.002) were associated with bacterial infection. All children with stool yielding diarrheagenic bacteria or C. difficile toxin had at least 1 of these factors, but so did 75% of children without these agents (positive predictive value, 11%; negative predictive value, 100%; sensitivity, 100%; specificity, 25%). Conclusions: The bacterial diarrhea prevalence is similar to that in other ambulatory studies, although the spectrum differs. Exclusion criteria for stool testing in diarrhea remain elusive. Studies to determine the etiology of unexplained diarrhea and cost-effective algorithms for diarrhea diagnosis, are needed.

The Centers for Disease Control and Prevention established the US National Tuberculosis Genotyping and Surveillance Network to study the utility of genotyping Mycobacterium tuberculosis isolates for prevention and control. From 1998 to 2000, four sites performed conventional contact investigations and epidemiologic investigations of cases with genotypically matched M. tuberculosis isolates, called cluster investigations. The authors compared cluster pairs (two cases with M. tuberculosis isolates having identical genotypes) whose epidemiologic linkages were discovered only during cluster investigation with those whose epidemiologic linkages were discovered during conventional contact investigation. Among the 2,141 reported culture-positive tuberculosis cases, 2,055 (96%) M. tuberculosis isolates were genotyped. By itself and at a minimum, cluster investigation added 43 (38%) of the 113 total epidemiologic linkages discovered. Of the epidemiologic linkages discovered during conventional contact investigation, 29% of tuberculosis case pairs were not supported by genotyping data. The linkages discovered only during cluster investigation were more likely discovered in nontraditional settings and relationships and among larger clusters (cluster size of >5: adjusted odds ratio = 57.6, 95% confidence interval: 31.8, 104.6). Information gained from genotyping M. tuberculosis isolates should initiate cluster investigations of tuberculosis cases not previously discovered as being epidemiologically linked during conventional contact investigation. Cluster investigations will play a crucial role in predicting recent tuberculosis transmission more accurately, as we move toward tuberculosis elimination in the United States.

We conducted a population-based study to assess demographic and risk-factor correlates for the most frequently occurring Mycobacterium tuberculosis genotypes from tuberculosis (TB) patients. The study included all incident, culture-positive TB patients from seven sentinel surveillance sites in the United States from 1996 to 2000. M. tuberculosis isolates were genotyped by IS6110-based restriction fragment length polymorphism and spoligotyping. Genotyping was available for 90% of 11,923 TB patients. Overall, 48% of cases had isolates that matched those from another patient, including 64% of U.S.-born and 35% of foreign-born patients. By logistic regression analysis, risk factors for clustering of genotypes were being male, U.S.-born, black, homeless, and infected with HIV; having pulmonary disease with cavitations on chest radiograph and a sputum smear with acid-fast bacilli; and excessive drug or alcohol use. Molecular characterization of TB isolates permitted risk correlates for clusters and specific genotypes to be described and provided information regarding cluster dynamics over time.

With more than 250,000 cases and 4,000 deaths in the first 6 months, the cholera epidemic in Haiti has been one of the most explosive and deadly in recent history. It is also one of the best documented, with detailed surveillance information available from the beginning of the epidemic, which allowed its spread to all parts of the country to be traced. Piarroux et al. make good use of this information, along with their own careful field investigations, to trace the epidemic to its beginning and propose an explanation for its origins (1). Multiple lines of evidence indicate that Vibrio cholerae was newly introduced into Haiti. Cholera had not been documented in Haiti for at least several generations. Although there was a reference to a small number of “cholera” cases during the American occupation in 1928 (2), there was no culture confirmation, and the likelihood is these represented cases of severe diarrhea caused by other pathogens. In the current situation, 14 V. cholerae isolates from the Artibonite Department early in the epidemic were indistinguishable by multiple phenotypic and molecular characterization methods, which indicated the infections were due to a single clone of V. cholerae introduced into Haiti in 1 event (3). Piarroux et al. present strong evidence that the earliest cases of cholera occurred in the upper Artibonite valley, near the town of Mirebalais (1). Within days of the Mirebalais cases, hundreds of additional cases were reported in the lower Artibonite valley, more than 50 km away, and over the next 2 days in neighboring departments outside the Artibonite valley. This rapid spread is characteristic of cholera transmission in a mobile, immunologically naive population with widespread exposure to sewage-contaminated drinking water. The mobility of the population ensured transmission of the pathogen to all 10 departments of Haiti within weeks, and the uniformly poor water and sanitation infrastructure ensured that where the pathogen was introduced local transmission would follow. Indeed, residents of the camps for internally displaced persons, where chlorinated water and sanitation was in many instances provided by outside organizations, experienced relatively low numbers of cholera infections (1). Piarroux et al. provide circumstantial evidence that fecal contamination of a local stream draining into the Artibonite River initiated the epidemic, that further spread then occurred to more heavily populated towns downstream in the river valley, and that a foreign peacekeeping battalion may have been the source of V. cholerae introduction into Haiti. The origin of cholera in Haiti is the subject of study by an independent panel appointed by the Secretary General of the United Nations. Certainly the spread within days to remote departments outside the valley indicates an important role for travel of infected persons along land routes in the subsequent if not the initial spread. However it occurred, there is little doubt that the organism was introduced to Haiti by a traveler from abroad, and this fact raises important public health considerations. Introduction into an immunologically naive population was necessary but not sufficient for such explosive epidemic spread. During the course of this epidemic, there were multiple introductions into camps for internally displaced persons in Haiti, with limited spread; into communities in the Dominican Republic, resulting in local but not widespread transmission; and into Florida and other states in the United States, with no secondary spread and no epidemics (4). These populations were also immunologically naive to cholera but were protected from exposure by physical and chemical barriers—the infrastructure for water treatment and distribution and for the collection and treatment of fecal waste—that effectively prevent contamination of food and drinking water by enteric pathogens. International travelers, including those going to serve vulnerable populations, are potential carriers of epidemic-prone disease. These travelers and their service organizations should take appropriate precautions (such as vaccination and chemoprophylaxis) to protect themselves and to forestall introducing such pathogens to local populations (5). After travelers’ arrival in a country, the spread of cholera and other enteric infections should be prevented by ensuring adequate sanitation such that pathogens excreted by either symptomatic or asymptomatic persons cannot be introduced into local food or water supplies. Prompt diagnosis and treatment of acute illnesses that may arise will also limit the opportunities for further spread. Realistically, however, it is impossible to completely guard against the introduction of infectious diseases, including cholera, into new populations and places, given the mobility of vast numbers of persons, animals, and products around the globe. For Haiti, the future course of the cholera epidemic is difficult to predict, especially given the chronic degradation of water and sanitation infrastructure over many years and the acute disruption from the earthquake in Haiti in January 2010 (6). Improving water and sanitation infrastructure is clearly the most effective and lasting approach to prevent the spread of cholera in countries where it is endemic as well as in those that are currently cholera-free. In the United States, Europe, and worldwide, disinfection of municipal water supplies and improvements in sanitation have dramatically reduced the incidence of cholera, typhoid, and overall mortality (7). In Haiti, the short-term public health response has included real-time surveillance, laboratory confirmation of infections, training of health workers on case management, and public education for basic cholera prevention. Enhanced access to medical services were scaled up quickly among many partner organizations by using the existing clinic infrastructure supported by the US President’s Emergency Plan for AIDS Relief. These efforts helped to reduce mortality to

Little is known about patterns of tuberculosis (TB) transmission among populations in developing countries with high rates of TB and human immunodeficiency virus (HIV) infection. To examine patterns of TB transmission in such a setting, we performed a population-based DNA fingerprinting study among TB patients in Botswana. Between January 1997 and July 1998, TB patients from four communities in Botswana were interviewed and offered HIV testing. Their Mycobacterium tuberculosis isolates underwent DNA fingerprinting using IS 6110 restriction fragment length polymorphism, and those with matching fingerprints were reinterviewed. DNA fingerprints with >5 bands were considered clustered if they were either identical or differed by at most one band, while DNA fingerprints with ≤5 bands were considered clustered only if they were identical. TB isolates of 125 (42%) of the 301 patients with completed interviews and DNA fingerprints fell into 20 different clusters of 2 to 16 patients. HIV status was not associated with clustering. Prior imprisonment was the only statistically significant risk factor for clustering (risk ratio, 1.5; 95% confidence interval, 1.1 to 2.0). In three communities where the majority of eligible patients were enrolled, 26 (11%) of 243 patients overall and 26 (25%) of 104 clustered patients shared both a DNA fingerprint and strong antecedent epidemiologic link. Most of the increasing TB burden in Botswana may be attributable to reactivation of latent infection, but steps should be taken to control ongoing transmission in congregate settings. DNA fingerprinting helps determine loci of TB transmission in the community.

Drug-susceptible and drug-resistant isolates of Mycobacterium tuberculosis were recovered from 2 patients, 1 with isoniazid-resistant tuberculosis (patient 1) and another with multidrug-resistant tuberculosis (patient 2). An investigation included patient interviews, record reviews, and genotyping of isolates. Both patients worked in a medical-waste processing plant. Transmission from waste was responsible for at least the multidrug-resistant infection. We found no evidence that specimens were switched or that cross-contamination of cultures occurred. For patient 1, susceptible and isoniazid-resistant isolates, collected 15 days apart, had 21 and 19 restriction fragments containing IS6110, 18 of which were common to both. For patient 2, a single isolate contained both drug-susceptible and multidrug-resistant colonies, demonstrating 10 and 11 different restriction fragments, respectively. These observations indicate that simultaneous infections with multiple strains of M. tuberculosis occur in immunocompetent hosts and may be responsible for conflicting drug-susceptibility results, though the circumstances of infections in these cases may have been unusual.

algorithm (shown in figure 1 in our article [2]) if they are serving a population with low or moderate prevalence (as defined in our article). We agree with Suputtamongkol et al. [6] that our approach may not be applicable in all settings. First, the most frequently detected pathogenic parasites (i.e., Srongyloides stercoralis, Cryptosporidium species, and Opisthorchis viverrini) listed in their report differ considerably from those reported in our study. Secondly, their stool ova and parasite procedure differs importantly from ours in that it does not include a general-purpose, permanently stained smear (e.g., GomoriWheatley trichrome, iron hematoxylin, or chlorazol black E stain), which aids in the detection of intestinal protozoa [7] and is a significant component of the comprehensive examination on which our findings and recommendations are based.

BackgroundMorgellons is a poorly characterized constellation of symptoms, with the primary manifestations involving the skin. We conducted an investigation of this unexplained dermopathy to characterize the clinical and epidemiologic features and explore potential etiologies.MethodsA descriptive study was conducted among persons at least 13 years of age and enrolled in Kaiser Permanente Northern California (KPNC) during 2006-2008. A case was defined as the self-reported emergence of fibers or materials from the skin accompanied by skin lesions and/or disturbing skin sensations. We collected detailed epidemiologic data, performed clinical evaluations and geospatial analyses and analyzed materials collected from participants' skin.ResultsWe identified 115 case-patients. The prevalence was 3.65 (95% CI = 2.98, 4.40) cases per 100,000 enrollees. There was no clustering of cases within the 13-county KPNC catchment area (p = .113). Case-patients had a median age of 52 years (range: 17-93) and were primarily female (77%) and Caucasian (77%). Multi-system complaints were common; 70% reported chronic fatigue and 54% rated their overall health as fair or poor with mean Physical Component Scores and Mental Component Scores of 36.63 (SD = 12.9) and 35.45 (SD = 12.89), respectively. Cognitive deficits were detected in 59% of case-patients and 63% had evidence of clinically significant somatic complaints; 50% had drugs detected in hair samples and 78% reported exposure to solvents. Solar elastosis was the most common histopathologic abnormality (51% of biopsies); skin lesions were most consistent with arthropod bites or chronic excoriations. No parasites or mycobacteria were detected. Most materials collected from participants' skin were composed of cellulose, likely of cotton origin.ConclusionsThis unexplained dermopathy was rare among this population of Northern California residents, but associated with significantly reduced health-related quality of life. No common underlying medical condition or infectious source was identified, similar to more commonly recognized conditions such as delusional infestation.

Summary From December 2005 through January 2006, the Minnesota Department of Health (MDH) identified four human clinical isolates of Salmonella Typhimurium that were indistinguishable by pulsed-field gel electrophoresis (PFGE). During routine interviews, three of the cases reported attending the same junior high school and two handled snakes in the science classroom. MDH collected environmental samples from the school’s science classroom for Salmonella culturing; these included environmental samples and frozen vacuum-packed mice purchased over the internet to feed the classroom snakes. Through PulseNet, a national molecular subtyping surveillance network for enteric bacteria, 21 human S. Typhimurium isolates with indistinguishable PFGE patterns were identified in the United States since December 2005. Each state determined whether these human cases had recent exposure to snakes fed vacuum-packed rodents. Texas state officials conducted tracebacks of the vacuum-packed mice and collected samples at the breeding facility. Nineteen of 21 cases were interviewed, and seven reported contact with frozen vacuum-packed rodents from the same internet-based supplier in Texas. In Minnesota, the outbreak PFGE subtype of S. Typhimurium was isolated from the snakes, frozen feed rodents, and the classroom environment. Three human cases were identified in Michigan, Pennsylvania, and Wyoming. The outbreak PFGE subtype of S. Typhimurium was isolated from the Pennsylvania case’s frozen rodents and the Michigan case’s pet snake. The outbreak PFGE subtype of S. Typhimurium was also isolated from the supplier’s rodent facility. This was a S. Typhimurium outbreak associated with frozen rodents. Human transmission likely occurred through direct contact with snakes and contaminated environmental surfaces. This report represents the second recent multi-state salmonellosis outbreak associated with commercially distributed rodents. Stronger oversight of the commercial rodent industry is warranted.

ContextBotulism is a potentially lethal paralytic disease caused primarily by toxins of the anaerobic, spore-forming bacterium Clostridium botulinum. Although botulinum toxin A is available by prescription for cosmetic and therapeutic use, no cases of botulism with detectable serum toxin have previously been attributed to cosmetic or therapeutic botulinum toxin injections. On November 27, 2004, 4 suspected botulism case-patients with a link to cosmetic botulinum toxin injections were reported to the Centers for Disease Control and Prevention.ObjectiveTo investigate the clinical, epidemiological, and laboratory aspects of 4 suspected cases of iatrogenic botulism.Design, Setting, and PatientsCase series on 4 botulism case-patients.Main Outcome MeasuresClinical characteristics of the 4 case-patients, epidemiological associations, and mouse bioassay neutralization test results from case-patient specimens and a toxin sample.ResultsClinical characteristics of the 4 case-patients were consistent with those of naturally occurring botulism. All case-patients had been injected with a highly concentrated, unlicensed preparation of botulinum toxin A and may have received doses 2857 times the estimated human lethal dose by injection. Pretreatment serum toxin levels in 3 of the 4 case-patients were equivalent to 21 to 43 times the estimated human lethal dose; pretreatment serum from the fourth epidemiologically linked case-patient was not available. A 100-μg vial of toxin taken from the same manufacturer's lot as toxin administered to the case-patients contained a toxin amount sufficient to kill approximately 14 286 adults by injection if disseminated evenly.ConclusionsThese laboratory-confirmed cases of botulism demonstrate that clinical use of unlicensed botulinum toxin A can result in severe, life-threatening illness. Further education and regulation are needed to prevent the inappropriate marketing, sale, and clinical use of unlicensed botulinum toxin products.

ContextWashington State has a relatively low incidence rate of tuberculosis (TB) infection. However, from May to September 1997, 3 cases of pulmonary TB were reported among medical waste treatment workers at 1 facility in Washington. There is no previous documentation of Mycobacterium tuberculosis transmission as a result of processing medical waste.ObjectiveTo identify the source(s) of these 3 TB infections.Design, Setting, and ParticipantsInterviews of the 3 infected patient-workers and their contacts, review of patient-worker medical records and the state TB registry, and collection of all multidrug-resistant TB (MDR-TB) isolates identified after January 1, 1995, from the facility's catchment area; DNA fingerprinting of all isolates; polymerase chain reaction and automated DNA sequencing to determine genetic mutations associated with drug resistance; and occupational safety and environmental evaluations of the facility.Main Outcome MeasuresPrevious exposures of patient-workers to TB; verification of patient-worker tuberculin skin test histories; identification of other cases of TB in the community and at the facility; drug susceptibility of patient-worker isolates; and potential for worker exposure to live M tuberculosis cultures.ResultsAll 3 patient-workers were younger than 55 years, were born in the United States, and reported no known exposures to TB. We did not identify other TB cases. The 3 patient-workers' isolates had different DNA fingerprints. One of 10 MDR-TB catchment-area isolates matched an MDR-TB patient-worker isolate by DNA fingerprint pattern. DNA sequencing demonstrated the same rare mutation in these isolates. There was no evidence of personal contact between these 2 individuals. The laboratory that initially processed the matching isolate sent contaminated waste to the treatment facility. The facility accepted contaminated medical waste where it was shredded, blown, compacted, and finally deactivated. Equipment failures, insufficient employee training, and respiratory protective equipment inadequacies were identified at the facility.ConclusionProcessing contaminated medical waste resulted in transmission of M tuberculosis to at least 1 medical waste treatment facility worker.

Objective. Between November 1994 and April 1995, more than 3300 students in 49 schools in two counties in New York were potentially exposed to five school bus drivers with tuberculosis. This investigation was carried out to determine the extent of transmission of Mycobacterium tuberculosis among students. Methods. Components of the epidemiologic investigation included tuberculin skin-test screening and collection of demographic information for students exposed to a driver with tuberculosis, chest radiography and medical evaluation of individuals with positive skin tests, and DNA fingerprinting of M tuberculosis isolates. A positive skin test was defined as ≥10 mm induration, and a converter was an individual with an increase in reaction size of ≥10 mm in the past 2 years. Results. The rates of positive skin tests were 0.8%, 0.3%, 9.9%, 1.1%, and 0.7% among US-born students exposed to drivers 1 through 5, respectively. The relative risk for a positive tuberculin skin test was significant only for students exposed to driver 3, and the only secondary case identified among students was exposed to driver 3. The DNA fingerprint patterns of isolates from drivers 3 and 4 matched. Conclusion. There was no clear evidence of transmission ofM tuberculosis to students from drivers 1, 2, 4, or 5. However, evidence suggests that driver 3 transmitted M tuberculosis to students and another driver. Routine annual tuberculin skin-test screening of drivers would not have prevented these tuberculosis exposures.