Typical enteropathogenic Escherichia coli (tEPEC) infection is a major cause of diarrhoea and contributor to mortality in children <5 years old in developing countries. Data were analysed from the Global Enteric Multicenter Study examining children <5 years old seeking care for moderate-to-severe diarrhoea (MSD) in Kenya. Stool specimens were tested for enteric pathogens, including by multiplex polymerase chain reaction for gene targets of tEPEC. Demographic, clinical and anthropometric data were collected at enrolment and ~60-days later; multivariable logistic regressions were constructed. Of 1778 MSD cases enrolled from 2008 to 2012, 135 (7.6%) children tested positive for tEPEC. In a case-to-case comparison among MSD cases, tEPEC was independently associated with presentation at enrolment with a loss of skin turgor (adjusted odds ratio (aOR) 2.08, 95% confidence interval (CI) 1.37–3.17), and convulsions (aOR 2.83, 95% CI 1.12–7.14). At follow-up, infants with tEPEC compared to those without were associated with being underweight (OR 2.2, 95% CI 1.3–3.6) and wasted (OR 2.5, 95% CI 1.3–4.6). Among MSD cases, tEPEC was associated with mortality (aOR 2.85, 95% CI 1.47–5.55). This study suggests that tEPEC contributes to morbidity and mortality in children. Interventions aimed at defining and reducing the burden of tEPEC and its sequelae should be urgently investigated, prioritised and implemented.

OBJECTIVES/SPECIFIC AIMS: This study seeks to test the feasibility and effectiveness of a brief Acceptance and commitment therapy (ACT) treatment for patients with persistent pain in a patient-centered medical home. METHODS/STUDY POPULATION: Participants are recruited via secure messaging, clinic advertisements and clinician referral. Primary care patients age 18 and older with at least 1 pain condition for 12 weeks or more in duration are stratified based on pain severity ratings and randomized into (a) ACT intervention or (b) control group [Enhanced Treatment as Usual (E-TAU)]. Participants in the ACT arm attend 1 individual visit with an integrated behavioral health provider, followed by 3 weekly ACT classes and a booster class 2 months later. E-TAU participants will receive usual care plus patient education handouts informed by cognitive behavioral science. Currently, 17% of our overall goal of 60 patients have completed ACT or enhanced treatment as usual. Average participant age is 49 years old, 70% female, and 70% Hispanic/Latino. Most report multisite pain conditions (e.g., musculoskeletal, fibromyalgia) and 30% are taking opioid medications. Data analysis in this presentation will include early correlational findings from baseline assessments. Upon study completion, we will analyze data using a general linear mixed regression model with repeated measures. RESULTS/ANTICIPATED RESULTS: The overall hypothesis is that brief ACT treatment reduces physical disability in patients with persistent pain when delivered by an integrated behavioral health provider in primary care. By examining a subset of patients on opioid medications, we also anticipate a reduction in opioid misuse behaviors. Additionally, it is anticipated that improvements in patient functioning will be mediated by patient change in pain acceptance and patient engagement in values-consistent behaviors. DISCUSSION/SIGNIFICANCE OF IMPACT: This pilot study will establish preliminary data about the feasibility and effectiveness of addressing persistent pain in a generalizable, “real-world” integrated primary care setting. Data will help support a larger trial in the future. If effective, findings could improve treatment methods and quality of life for patients with persistent pain using a scalable approach.

Given the challenges in accurately identifying unexposed controls in case–control studies of diarrhoea, we examined diarrhoea incidence, subclinical enteric infections and growth stunting within a reference population in the Global Enteric Multicenter Study, Kenya site. Within ‘control’ children (0–59 months old without diarrhoea in the 7 days before enrolment, n = 2384), we examined surveys at enrolment and 60-day follow-up, stool at enrolment and a 14-day post-enrolment memory aid for diarrhoea incidence. At enrolment, 19% of controls had ⩾1 enteric pathogen associated with moderate-to-severe diarrhoea (‘MSD pathogens’) in stool; following enrolment, many reported diarrhoea (27% in 7 days, 39% in 14 days). Controls with and without reported diarrhoea had similar carriage of MSD pathogens at enrolment; however, controls reporting diarrhoea were more likely to report visiting a health facility for diarrhoea (27% vs. 7%) or fever (23% vs. 16%) at follow-up than controls without diarrhoea. Odds of stunting differed by both MSD and ‘any’ (including non-MSD pathogens) enteric pathogen carriage, but not diarrhoea, suggesting control classification may warrant modification when assessing long-term outcomes. High diarrhoea incidence following enrolment and prevalent carriage of enteric pathogens have implications for sequelae associated with subclinical enteric infections and for design and interpretation of case–control studies examining diarrhoea.

OBJECTIVES/SPECIFIC AIMS: This study seeks to test the feasibility and effectiveness of a brief acceptance and commitment therapy (ACT) treatment for chronic pain patients in a primary care clinic METHODS/STUDY POPULATION: Primary care patients aged 18 years and older with at least 1 pain condition for 12 weeks or more in duration will be recruited. Patients will be randomized into (a) ACT intervention or (b) control group. Participants in the ACT arm will attend 1 individual visit with an integrated behavioral health provider, followed by 3 weekly ACT classes and a booster class 2 months later. Control group will receive enhanced primary care that includes patient education handouts informed by cognitive behavioral science. Data analysis will include 1-way analysis of covariance (ANCOVA), multiple regression with bootstrapping. RESULTS/ANTICIPATED RESULTS: The overall hypothesis is that brief ACT treatment reduces physical disability, improves functioning, and reduces medication misuse in chronic pain patients when delivered by an integrated behavioral health provider in primary care. In addition, it is anticipated that improvements in patient functioning will be mediated by patient change in pain acceptance and patient engagement in value-consistent behaviors. DISCUSSION/SIGNIFICANCE OF IMPACT: This pilot study will establish preliminary data about the effectiveness of addressing chronic pain in a generalizable integrated primary care setting. Data will help support a larger trial in the future. Findings have potential to transform the way chronic pain is currently managed in primary care settings, with results that could decrease disability and improve functioning among patients suffering from chronic pain.

Obtaining accurate age determinations from minerals in archaeological ash is a major unsolved issue in radiocarbon (14C) dating. This is because the original 14C content of calcite, the main component of ash, is altered by isotopic exchange. Pyrogenic aragonite, another mineral phase recently discovered in ash, might preserve its 14C signature through time. Using a new method based on density separation and step combustion, we were able to isolate and date aragonitic ash from an archaeological destruction horizon of known age. Here we show that the 14C age of aragonite matches the age of the destruction horizon. Our results demonstrate that pyrogenic aragonite is a short-lived material suitable for 14C dating and directly related to human activities involving the use of fire, thus bearing major implications for the establishment of absolute chronologies for the past 50,000 yr.

Although rare, typhoid fever cases acquired in the United States continue to be reported. Detection and investigation of outbreaks in these domestically acquired cases offer opportunities to identify chronic carriers. We searched surveillance and laboratory databases for domestically acquired typhoid fever cases, used a space–time scan statistic to identify clusters, and classified clusters as outbreaks or non-outbreaks. From 1999 to 2010, domestically acquired cases accounted for 18% of 3373 reported typhoid fever cases; their isolates were less often multidrug-resistant (2% vs. 15%) compared to isolates from travel-associated cases. We identified 28 outbreaks and two possible outbreaks within 45 space–time clusters of ⩾2 domestically acquired cases, including three outbreaks involving ⩾2 molecular subtypes. The approach detected seven of the ten outbreaks published in the literature or reported to CDC. Although this approach did not definitively identify any previously unrecognized outbreaks, it showed the potential to detect outbreaks of typhoid fever that may escape detection by routine analysis of surveillance data. Sixteen outbreaks had been linked to a carrier. Every case of typhoid fever acquired in a non-endemic country warrants thorough investigation. Space–time scan statistics, together with shoe-leather epidemiology and molecular subtyping, may improve outbreak detection.

US cholera surveillance offers insight into global and domestic trends. Between 2001 and 2011, 111 cases were reported to the Centers for Disease Control and Prevention. Cholera was associated with international travel in 90 (81%) patients and was domestically acquired in 20 (18%) patients; for one patient, information was not available. From January 2001 to October 2010, the 42 (47%) travel-associated cases were associated with travel to Asia. In October 2010, a cholera epidemic started in Haiti, soon spreading to the Dominican Republic (Hispaniola). From then to December 2011, 40 (83%) of the 48 travel-associated cases were associated with travel to Hispaniola. Of 20 patients who acquired cholera domestically, 17 (85%) reported seafood consumption; 10 (59%) ate seafood from the US Gulf Coast. In summary, an increase in travel-associated US cholera cases was associated with epidemic cholera in Hispaniola in 2010–2011. Travel to Asia and consumption of Gulf Coast seafood remained important sources of US cholera cases.

Cameroon has experienced recurrent cholera epidemics with high mortality rates. In September 2009, epidemic cholera was detected in the Far North region of Cameroon and the reported case-fatality rate was 12%. We conducted village-, healthcare facility- and community-level surveys to investigate reasons for excess cholera mortality. Results of this investigation suggest that cholera patients who died were less likely to seek care, receive rehydration therapy and antibiotics at a healthcare facility, and tended to live further from healthcare facilities. Furthermore, use of oral rehydration salts at home was very low in both decedents and survivors. Despite the many challenges inherent to delivering care in Cameroon, practical measures could be taken to reduce cholera mortality in this region, including the timely provision of treatment supplies, training of healthcare workers, establishment of rehydration centres, and promotion of household water treatment and enhanced handwashing with soap.

The emergence of epidemic cholera in post-earthquake Haiti portended a public health disaster of uncertain magnitude. In order to coordinate relief efforts in an environment with limited healthcare infrastructure and stretched resources, timely and realistic projections of the extent of the cholera outbreak were crucial. Projections were shared with Government and partner organizations beginning 5 days after the first reported case and were updated using progressively more advanced methods as more surveillance data became available. The first projection estimated that 105 000 cholera cases would occur in the first year. Subsequent projections using different methods estimated up to 652 000 cases and 163 000–247 000 hospitalizations during the first year. Current surveillance data show these projections to have provided reasonable approximations of the observed epidemic. Providing the real-time projections allowed Haitian ministries and external aid organizations to better plan and implement response measures during the evolving epidemic.

We examined reported outbreaks of foodborne shigellosis in the USA from 1998 to 2008 and summarized demographic and epidemiological characteristics of 120 confirmed outbreaks resulting in 6208 illnesses. Most reported foodborne shigellosis outbreaks (n = 70, 58%) and outbreak-associated illnesses (n = 3383, 54%) were restaurant-associated. The largest outbreaks were associated with commercially prepared foods distributed in multiple states and foods prepared in institutional settings. Foods commonly consumed raw were implicated in 29 (24%) outbreaks and infected food handlers in 28 (23%) outbreaks. Most outbreaks (n = 86, 72%) were caused by Shigella sonnei. Targeted efforts to reduce contamination during food handling at multiple points in the food processing and distribution system, including food preparation in restaurants and institutional settings, could prevent many foodborne disease outbreaks and outbreak-related illnesses including those due to Shigella.

To determine risk factors for cholera in an epidemic-disease area in South America, a case–control investigation was performed in Guayaquil, Ecuador, in July 1991. Residents > 5 years old who were hospitalized for treatment of acute, watery diarrhoea and two matched controls for each were interviewed regarding sources of water and food, and eating, drinking, and hygienic habits. Interviewers inspected homes of case-patients and controls to document water treatment, food-handling, and hygienic practices. Faecal specimens and shellfish were cultured for Vibrio cholerae O 1. Isolates were tested for susceptibility to a variety of antimicrobial agents. Drinking unboiled water (odds ratio [OR] = 4.0, confidence interval [CI] = 1.8–7.5), drinking a beverage from a street vendor (OR = 2.8, CI = 1.3–5.9), eating raw seafood (OR = 3.4, CI = 1.4–11.5), and eating cooked crab (OR = 5.1, CI = 1.4–19.2) were associated with illness. Always boiling drinking water at home (OR = 0.5, CI = 0.2–0.9) was protective against illness. The presence of soap in either the kitchen (OR = 0.3, CI = 0.2–0.8) or bathroom (OR = 0.4, CI = 0.2–0.9) at home was also protective. V. cholerae O 1 was recovered from a pooled sample of a bivalve mollusc and from 68% of stool samples from case-patients. Thirty-six percent of the isolates from stool specimens were resistant to multiple antimicrobial agents. Specific prevention measures may prevent transmission through these vehicles in the future. The appearance of antimicrobial resistance suggests the need for changes in current methods of prevention and treatment.

The effects of ingested Salmonella enteritidis (SE) dose on incubation period and on the severity and duration of illness were estimated in a cohort of 169 persons who developed gastroenteritis after eating hollandaise sauce made from grade–A shell eggs. The cohort was divided into three groups based on self–reported dose of sauce ingested. As dose increased, median incubation period decreased (37 h in the low exposure group 21 h in the medium exposure group v. 17·5 h. in the high exposure group, P = 0.006) and greater proportions reported body aches (71 v. 85 v. 94%, P = 0.0009) and vomiting (21 v. 56 v. 57%, P = 0.002). Among 118 case-persons who completed a follow–up questionnaire, increased dose was associated with increases in median weight loss in kilograms (3.2 v. 4.5 v. 5.0, P = 0.0001), maximum daily number of stools (12.5 v. 15.0 v. 20.0, P = 0.02), subjective rating of illness severity (P = 0.0007), and the number of days of confinement to bed (3.0 v. 6.5, P = 0.04). In this outbreak, ingested dose was an important determinant of the incubation period, symptoms and severity of acute salmonellosis.

During 22–24 August 2004, an outbreak of Shigella sonnei infection affected air travellers who departed from Hawaii. Forty-seven passengers with culture-confirmed shigellosis and 116 probable cases who travelled on 12 flights dispersed to Japan, Australia, 22 US states, and American Samoa. All flights were served by one caterer. Pulsed-field gel electrophoresis of all 29 S. sonnei isolates yielded patterns that matched within one band. Food histories and menu reviews identified raw carrot served onboard as the likely vehicle of infection. Attack rates for diarrhoea on three surveyed flights with confirmed cases were 54% (110/204), 32% (20/63), and 12% (8/67). A total of 2700 meals were served on flights with confirmed cases; using attack rates observed on surveyed flights, we estimated that 300–1500 passengers were infected. This outbreak illustrates the risk of rapid, global spread of illness from a point-source at a major airline hub.

Enterotoxigenic Escherichia coli (ETEC) is a common cause of profuse watery diarrhoea in the developing world, often leading to severe dehydration or death. We found only 15 population-based studies in low and medium human development index (HDI) countries from 1984 to 2005 that evaluate disease incidence. Reported incidence ranged from 39 to 4460 infections/1000 persons per year. The peak incidence of ETEC appeared to occur between ages 6 and 18 months. A median of 14% (range 2–36%) of diarrhoeal specimens were positive for ETEC in 19 facility- and population-based studies conducted in all age groups and 13% (range 3–39%) in 51 studies conducted in children only. Heat-labile toxin (LT)-ETEC is thought to be less likely to cause disease than heat-stable toxin (ST)-ETEC or LT/ST-ETEC. Because population-based studies involve enhanced clinical management of patients and facility-based studies include only the most severe illnesses, reliable data on complications and mortality from ETEC infections was unavailable. To reduce gaps in the current understanding of ETEC incidence, complications and mortality, large population-based studies combined with facility-based studies covering a majority of the corresponding population are needed, especially in low-HDI countries. Moreover, a standard molecular definition of ETEC infection is needed to be able to compare results across study sites.

The global incidence of Shigella infection has been estimated at 80–165 million episodes annually, with 99% of episodes occurring in the developing world. To identify contemporary gaps in the understanding of the global epidemiology of shigellosis, we conducted a review of the English-language scientific literature from 1984 to 2005, restricting the search to low and medium human development countries. Our review yielded 11 population-based studies of Shigella burden from seven countries. No population-based studies have been conducted in sub-Saharan Africa or in low human development countries. In studies done in all age groups, Shigella incidence varied from 0·6 to 107 episodes/1000 person-years. S. flexneri was the most commonly detected subgroup in the majority of studies. Case-fatality rates ranged from 0% to 2·6% in population-based studies and from 0% to 21% in facility-based studies. This review highlights the large gaps in data on the burden of Shigella infections for low human development index countries and, more specifically, for sub-Saharan Africa.

There are only 10 contemporary, population-based studies of typhoid fever that evaluate disease incidence using blood culture for confirmation of cases. Reported incidence ranged from 13 to 976/100 000 persons per year. These studies are likely to have been done preferentially in high- incidence sites which makes generalization of data difficult. Only five of these studies reported mortality. Of these the median (range) mortality was 0% (0–1·8%). Since study conditions usually involved enhanced clinical management of patients and the studies were not designed to evaluate mortality as an outcome, their usefulness for generalizing case-fatality rates is uncertain. No contemporary population-based studies reported rates of complications. Hospital-based typhoid fever studies reported median (range) complication rates of 2·8% (0·6–4·9%) for intestinal perforation and case-fatality rates of 2·0% (0–14·8%). Rates of complications other than intestinal perforation were not reported in contemporary hospital-based studies. Hospital-based studies capture information on the most severe illnesses among persons who have access to health-care services limiting their generalizability. Only two studies have informed the current understanding of typhoid fever age distribution curves. Extrapolation from population-based studies suggests that most typhoid fever occurs among young children in Asia. To reduce gaps in the current understanding of typhoid fever incidence, complications, and case-fatality rate, large population-based studies using blood culture confirmation of cases are needed in representative sites, especially in low and medium human development index countries outside Asia.

We systematically investigated risk factors for typhoid fever in Kamalapur, a poor urban area of Bangladesh, to inform targeted public health measures for its control. We interviewed patients with typhoid fever and two age-matched controls per case about exposures during the 14 days before the onset of illness. The municipal water supply was used by all 41 cases and 81of 82 controls. In multivariate analysis, drinking unboiled water at home was a significant risk factor [adjusted odds ratio (aOR) 12·1, 95% CI 2·2–65·6]. Twenty-three (56%) cases and 21 (26%) controls reported that water from the primary source was foul-smelling (aOR 7·4, 95% CI 2·1–25·4). Eating papaya was associated with illness (aOR 5·2, 95% CI 1·2–22·2). Using a latrine for defecation was significantly protective (aOR 0·1, 95% CI 0·02–0·9). Improved chlorination of the municipal water supply or disinfecting drinking water at the household level may dramatically reduce the risk of typhoid fever in Kamalapur. The protective effect of using latrines, particularly among young children, should be investigated further.