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Summary Botulism is a rare, neurotoxin-mediated, life-threatening disease characterized by flaccid descending paralysis that begins with cranial nerve palsies and might progress to extremity weakness and respiratory failure. Botulinum neurotoxin, which inhibits acetylcholine release at the neuromuscular junction, is produced by the anaerobic, gram-positive bacterium Clostridium botulinum and, rarely, by related species (C. baratii and C. butyricum). Exposure to the neurotoxin occurs through ingestion of toxin (foodborne botulism), bacterial colonization of a wound (wound botulism) or the intestines (infant botulism and adult intestinal colonization botulism), and high-concentration cosmetic or therapeutic injections of toxin (iatrogenic botulism). In addition, concerns have been raised about the possibility of a bioterrorism event involving toxin exposure through intentional contamination of food or drink or through aerosolization. Neurologic symptoms are similar regardless of exposure route. Treatment involves supportive care, intubation and mechanical ventilation when necessary, and administration of botulinum antitoxin. Certain neurological diseases (e.g., myasthenia gravis and Guillain-Barré syndrome) have signs and symptoms that overlap with botulism. Before the publication of these guidelines, no comprehensive clinical care guidelines existed for treating botulism. These evidence-based guidelines provide health care providers with recommended best practices for diagnosing, monitoring, and treating single cases or outbreaks of foodborne, wound, and inhalational botulism and were developed after a multiyear process involving several systematic reviews and expert input.

Background Coronavirus disease 2019 (COVID-19) causes a range of illness severity. Mild illness has been reported, but whether illness severity correlates with infectivity is unknown. We describe the public health investigation of a mildly ill, nonhospitalized COVID-19 case who traveled to China. Methods The case was a Maricopa County resident with multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–positive specimens collected on 22 January 2020. Contacts were persons exposed to the case on or after the day before case diagnostic specimen collection. Contacts were monitored for 14 days after last known exposure. High-risk contacts had close, prolonged case contact (≥ 10 minutes within 2 m). Medium-risk contacts wore all US Centers for Disease Control and Prevention–recommended personal protective equipment during interactions. Nasopharyngeal and oropharyngeal (NP/OP) specimens were collected from the case and high-risk contacts and tested for SARS-CoV-2. Results Paired case NP/OP specimens were collected for SARS-CoV-2 testing at 11 time points. In 8 pairs (73%), ≥ 1 specimen tested positive or indeterminate, and in 3 pairs (27%) both tested negative. Specimens collected 18 days after diagnosis tested positive. Sixteen contacts were identified; 11 (69%) had high-risk exposure, including 1 intimate contact, and 5 (31%) had medium-risk exposure. In total, 35 high-risk contact NP/OP specimens were collected for SARS-CoV-2 testing; all 35 pairs (100%) tested negative. Conclusions This report demonstrates that SARS-CoV-2 infection can cause mild illness and result in positive tests for up to 18 days after diagnosis, without evidence of transmission to close contacts. These data might inform public health strategies to manage individuals with asymptomatic infection or mild illness.

Botulism is typically described as a rapidly progressing, severe neuroparalytic disease. Foodborne botulism is transmitted through consuming food or drink that has been contaminated with botulinum toxin. During a botulism outbreak linked to illicitly brewed alcohol (also known as “hooch” or “pruno”) in a prison, 11 (35%) of 31 inmates that consumed contaminated hooch had mild illnesses. This includes 2 inmates with laboratory confirmed botulism. The most frequently reported signs and symptoms among the 11 patients with mild illness included dry mouth (91%), hoarse voice (91%), difficulty swallowing (82%), fatigue (82%), and abdominal pain (82%). Foodborne botulism is likely underdiagnosed and underreported in patients with mild illness. Botulism should be considered on the differential diagnosis for patients with cranial nerve palsies.

Clostridium botulinum produces botulinum neurotoxin (BoNT), which can lead to death if untreated. In the United States, over 90% of wound botulism cases are associated with injection drug use of black tar heroin. We sought to determine the phylogenetic relatedness of C. botulinum isolated from an injection drug use wound botulism case and isolates from endogenous infant botulism cases in Hawaii. Nineteen C. botulinum type B isolates from Hawaii and one type B isolate from California were analyzed by whole-genome sequencing. The botulinum toxin gene (bont) subtype was determined using CLC Genomics Workbench, and the seven-gene multi-locus sequence type (MLST) was identified by querying PubMLST. Mashtree and pairwise average nucleotide identity were used to find nearest neighbors, and Lyve-SET approximated a phylogeny. Eighteen of the isolates harbored the bont/B5 gene: of those, 17 were classified as sequence type ST36 and one was classified as ST104. A single isolate from Hawaii harbored bont/B1 and was determined to belong to ST110, and the isolate from California harbored bont/B1 and belonged to ST30. A tree constructed with Lyve-SET showed a high degree of homology among all the Hawaiian C. botulinum isolates that harbor the bont/B5 gene. Our results indicate that the bont/B-expressing isolates recovered from Hawaii are closely related to each other, suggesting local contamination of the drug paraphernalia or the wound itself with spores rather than contamination of the drug at manufacture or during transport. These findings may assist in identifying interventions to decrease wound botulism among persons who inject drugs.

CDC, the Food and Drug Administration (FDA), state and local health departments, and public health and clinical stakeholders are investigating a nationwide outbreak of e-cigarette, or vaping, product use-associated lung injury (EVALI) (1). As of November 13, 2019, 49 states, the District of Columbia, and two U.S. territories (Puerto Rico and U.S. Virgin Islands) have reported 2,172 EVALI cases to CDC, including 42 (1.9%) EVALI-associated deaths. To inform EVALI surveillance, including during the 2019-20 influenza season, case report information supplied by states for hospitalized and nonhospitalized patients with EVALI were analyzed using data collected as of November 5, 2019. Among 2,016 EVALI patients with available data on hospitalization status, 1,906 (95%) were hospitalized, and 110 (5%) were not hospitalized. Demographic characteristics of hospitalized and nonhospitalized patients were similar; most were male (68% of hospitalized versus 65% of nonhospitalized patients), and most were aged

Background As of January 7, 2020, a total of 2558 hospitalized patients with nonfatal cases and 60 patients with fatal cases of e-cigarette, or vaping, product use-associated lung injury (EVALI) had been reported to the Centers for Disease Control and Prevention (CDC). Methods In a national study, we compared the characteristics of patients with fatal cases of EVALI with those of patients with nonfatal cases to improve the ability of clinicians to identify patients at increased risk for death from the condition. Health departments reported cases of EVALI to the CDC and included, when available, data from medical-record abstractions and patient interviews. Analyses included all the patients with fatal or nonfatal cases of EVALI that were reported to the CDC as of January 7, 2020. We also present three case reports of patients who died from EVALI to illustrate the clinical characteristics common among such patients. Results Most of the patients with fatal or nonfatal cases of EVALI were male (32 of 60 [53%] and 1666 of 2498 [67%], respectively). The proportion of patients with fatal or nonfatal cases was higher among those who were non-Hispanic white (39 of 49 [80%] and 1104 of 1818 [61%], respectively) than among those in other race or ethnic groups. The proportion of patients with fatal cases was higher among those 35 years of age or older (44 of 60 [73%]) than among those younger than 35 years, but the proportion with nonfatal cases was lower among those 35 years of age or older (551 of 2514 [22%]). Among the patients who had an available medical history, a higher proportion of those with fatal cases than those with nonfatal cases had a history of asthma (13 of 57 [23%] vs. 102 of 1297 [8%]), cardiac disease (26 of 55 [47%] vs. 115 of 1169 [10%]), or a mental health condition (32 of 49 [65%] vs. 575 of 1398 [41%]). A total of 26 of 50 patients (52%) with fatal cases had obesity. Half the patients with fatal cases (25 of 54 [46%]) were seen in an outpatient setting before hospitalization or death. Conclusions Chronic conditions, including cardiac and respiratory diseases and mental health conditions, were common among hospitalized patients with EVALI.

IntroductionMore than 93,000 cases of coronavirus disease (COVID-19) have been reported worldwide. We describe the epidemiology, clinical course, and virologic characteristics of the first 12 U.S. patients with COVID-19.MethodsWe collected demographic, exposure, and clinical information from 12 patients confirmed by CDC during January 20–February 5, 2020 to have COVID-19. Respiratory, stool, serum, and urine specimens were submitted for SARS-CoV-2 rRT-PCR testing, virus culture, and whole genome sequencing.ResultsAmong the 12 patients, median age was 53 years (range: 21–68); 8 were male, 10 had traveled to China, and two were contacts of patients in this series. Commonly reported signs and symptoms at illness onset were fever (n=7) and cough (n=8). Seven patients were hospitalized with radiographic evidence of pneumonia and demonstrated clinical or laboratory signs of worsening during the second week of illness. Three were treated with the investigational antiviral remdesivir. All patients had SARS-CoV-2 RNA detected in respiratory specimens, typically for 2–3 weeks after illness onset, with lowest rRT-PCR Ct values often detected in the first week. SARS-CoV-2 RNA was detected after reported symptom resolution in seven patients. SARS-CoV-2 was cultured from respiratory specimens, and SARS-CoV-2 RNA was detected in stool from 7/10 patients.ConclusionsIn 12 patients with mild to moderately severe illness, SARS-CoV-2 RNA and viable virus were detected early, and prolonged RNA detection suggests the window for diagnosis is long. Hospitalized patients showed signs of worsening in the second week after illness onset.

Coronavirus disease 2019 (COVID-19), the respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first identified in Wuhan, China and has since become pandemic. In response to the first cases identified in the United States, close contacts of confirmed COVID-19 cases were investigated to enable early identification and isolation of additional cases and to learn more about risk factors for transmission. Close contacts of nine early travel-related cases in the United States were identified and monitored daily for development of symptoms (active monitoring). Selected close contacts (including those with exposures categorized as higher risk) were targeted for collection of additional exposure information and respiratory samples. Respiratory samples were tested for SARS-CoV-2 by real-time reverse transcription polymerase chain reaction at the Centers for Disease Control and Prevention. Four hundred four close contacts were actively monitored in the jurisdictions that managed the travel-related cases. Three hundred thirty-eight of the 404 close contacts provided at least basic exposure information, of whom 159 close contacts had ≥1 set of respiratory samples collected and tested. Across all actively monitored close contacts, two additional symptomatic COVID-19 cases (i.e., secondary cases) were identified; both secondary cases were in spouses of travel-associated case patients. When considering only household members, all of whom had ≥1 respiratory sample tested for SARS-CoV-2, the secondary attack rate (i.e., the number of secondary cases as a proportion of total close contacts) was 13% (95% CI: 4-38%). The results from these contact tracing investigations suggest that household members, especially significant others, of COVID-19 cases are at highest risk of becoming infected. The importance of personal protective equipment for healthcare workers is also underlined. Isolation of persons with COVID-19, in combination with quarantine of exposed close contacts and practice of everyday preventive behaviors, is important to mitigate spread of COVID-19.

In April 2015, a multistate outbreak of illness linked to synthetic cannabinoid (SC) use was unprecedented in magnitude and severity. We identified Mississippi cases in near-real time, collected information on cases to characterize the outbreak, and identified the causative SC.A case was defined as any patient of a Mississippi healthcare facility who was suspected of SC use and presenting with ≥2 of the following symptoms: sweating, severe agitation, or psychosis during April 2-May 3, 2015. Clinicians reported cases to the Mississippi Poison Control Center (MPCC). We used MPCC data to identify cases at the University of Mississippi Medical Center (UMMC) to characterize in further detail, including demographics and clinical findings. Biologic samples were tested for known and unknown SCs by liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF/MS).Clinicians reported 721 cases (11 deaths) statewide; 119 (17%) were UMMC patients with detailed data for further analysis. Twelve (10%) were admitted to an intensive care unit and 2 (2%) died. Aggression (32%), hypertension (33%), and tachycardia (42%) were common. SCs were identified in serum from 39/56 patients (70%); 33/39 patients (85%) tested positive for MAB-CHMINACA (N-(1-amino-3,3-dimethyl-1-oxobutan-2-yl)-1-(cyclohexylmethyl)-1H-indazole-3-carboxamide) or its metabolites. Compared to all patients tested for SCs, those positive for MAB-CHMINACA were more likely to have altered mental status on examination (OR = 3.3, p = .05).SC use can cause severe health effects. MAB-CHMINACA was the most commonly detected SC in this outbreak. As new SCs are created, new strategies to optimize surveillance and patient care are needed to address this evolving public health threat.

In February 2018, a typhoid fever outbreak caused by Salmonella enterica serotype Typhi (Typhi), resistant to chloramphenicol, ampicillin, trimethoprim-sulfamethoxazole, fluoroquinolones, and third-generation cephalosporins, was reported in Pakistan. During November 2016-September 2017, 339 cases of this extensively drug-resistant (XDR) Typhi strain were reported in Pakistan, mostly in Karachi and Hyderabad; one travel-associated case was also reported from the United Kingdom (1). More cases have been detected in Karachi and Hyderabad as surveillance efforts have been strengthened, with recent reports increasing the number of cases to 5,372 (2). In the United States, in response to the reports from Pakistan, enhanced surveillance identified 29 patients with typhoid fever who had traveled to or from Pakistan during 2016-2018, including five with XDR Typhi. Travelers to areas with endemic disease, such as South Asia, should be vaccinated against typhoid fever before traveling and follow safe food and water practices. Clinicians should be aware that most typhoid fever infections in the United States are fluoroquinolone nonsusceptible and that the XDR Typhi outbreak strain associated with travel to Pakistan is only susceptible to azithromycin and carbapenems.

Background Botulism is a rare, potentially fatal paralytic illness caused by neurotoxins. To inform the evaluation of patients with suspected botulism, we conducted a systematic review to describe the clinical features of botulism. Methods We searched Medline Ovid, Embase Dialog, Embase Ovid, Cumulative Index to Nursing and Allied Health Literature (CINAHL) EBSCO, Global Health Ovid, Cochrane Library, Scopus, and ClinicalTrials.gov for English language articles through May 2015. Information abstracted included demographics, signs and symptoms, laboratory results, and clinical outcome for foodborne and wound botulism patients confirmed by laboratory testing, epidemiologic link, or association with an outbreak. The review followed PRISMA guidelines and was registered with PROSPERO (CRD42015024784). Results We identified 402 patients from 233 articles published in English between 1932 and 2015. Most cases (n = 346 [86%]) were foodborne botulism and most (n = 263 [65%]) were associated with an outbreak. The median incubation period was 1 day, and the median time from illness onset to hospital admission was 2 days. Shortness of breath, dyspnea, or respiratory distress or failure at hospital admission was reported in 169 (42%) patients; 71 (42%) reported respiratory involvement without report of extremity weakness. Among 154 patients for whom the hospital day of intubation was reported, 134 (87%) were intubated on the first or second hospital day. Conclusions Botulism patients can experience a range of signs and symptoms. Respiratory involvement may occur early in the illness and can occur without preceding extremity weakness. Clinicians and public health departments preparing for and responding to botulism events should use this information to guide the evaluation of suspected botulism patients.

Effective treatment for botulism requires early clinical recognition. Diagnosis of botulism, including during outbreaks, can be challenging. We assessed combinations of signs and symptoms among confirmed cases and identified sensitive clinical criteria to trigger suspicion. We produced a tool that may facilitate rapid identification of sporadic and outbreak-associated cases.

Background We performed a systematic review of foodborne botulism outbreaks to describe their clinical aspects and descriptive epidemiology in order to inform public health response strategies. Methods We searched seven databases for reports of foodborne botulism outbreaks published in English from database inception to May 2015. We summarized descriptive characteristics and analyzed differences in exposure and toxin types by geographic region. We performed logistic regression to assess correlations between exposure source, implicated food, and outbreak size. Results There were 197 outbreaks reported between 1920 and 2014. The median number of cases per outbreak was 3 (range 2-97). The majority of reported outbreaks (109; 55%) occurred in the United States. Toxin types A, B, E, and F were identified as the causative agent in 34%, 16%, 17%, and 1% of outbreaks, respectively. The median duration between exposure and symptom onset was approximately 1 day. The mean percentage of cases requiring mechanical ventilation per outbreak was 34%. Seventy percent of all outbreaks and 77% of small outbreaks (≤11 cases) originated from point source exposures, while commercial foods were significantly (odds ratio, 6.9; 95% confidence interval, 2.2-21.1) associated with large outbreaks (≥12 cases). Conclusions Toxin type A accounted for half of outbreaks, and these outbreaks had a higher proportion of patient ventilatory failure. Most outbreaks were due to point source exposures, while outbreaks due to commercial food were larger. For effective responses to foodborne botulism outbreaks, these findings demonstrate the need for timely outbreak investigation and hospital surge capacity.

In September 2013, the Hawaii Department of Health (HDOH) was notified of seven adults who developed acute hepatitis after taking OxyELITE Pro™, a weight loss and sports dietary supplement. CDC assisted HDOH with their investigation, then conducted case-finding outside of Hawaii with FDA and the Department of Defense (DoD). We defined cases as acute hepatitis of unknown etiology that occurred from April 1, 2013, through December 5, 2013, following exposure to a weight loss or muscle-building dietary supplement, such as OxyELITE Pro™. We conducted case-finding through multiple sources, including data from poison centers (National Poison Data System [NPDS]) and FDA MedWatch. We identified 40 case-patients in 23 states and two military bases with acute hepatitis of unknown etiology and exposure to a weight loss or muscle building dietary supplement. Of 35 case-patients who reported their race, 15 (42.9%) reported white and 9 (25.7%) reported Asian. Commonly reported symptoms included jaundice, fatigue, and dark urine. Twenty-five (62.5%) case-patients reported taking OxyELITE Pro™. Of these 25 patients, 17 of 22 (77.3%) with available data were hospitalized and 1 received a liver transplant. NPDS and FDA MedWatch each captured seven (17.5%) case-patients. Improving the ability to search surveillance systems like NPDS and FDA MedWatch for individual and grouped dietary supplements, as well as coordinating case-finding with DoD, may benefit ongoing surveillance efforts and future outbreak responses involving adverse health effects from dietary supplements. This investigation highlights opportunities and challenges in using multiple sources to identify cases of suspected supplement associated adverse events. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

E-cigarette use is increasing, and the long-term impact on public health is unclear. We described the acute adverse health effects from e-cigarette exposures reported to U.S. poison centers. We compared monthly counts and demographic, exposure, and health effects data of calls about e-cigarettes and conventional cigarettes made to poison centers from September 2010 through December 2014. Monthly e-cigarette calls increased from 1 in September 2010, peaked at 401 in April 2014, and declined to 295 in December 2014. Monthly conventional cigarette calls during the same period ranged from 302 to 514. E-cigarette calls were more likely than conventional cigarette calls to report adverse health effects, including vomiting, eye irritation, and nausea. Five e-cigarette calls reported major health effects, such as respiratory failure, and there were two deaths associated with e-cigarette calls. E-cigarette calls to U.S. poison centers increased over the study period, and were more likely than conventional cigarettes to report adverse health effects. It is important for health care providers and the public to be aware of potential acute health effects from e-cigarettes. Developing strategies to monitor and prevent poisonings from these novel devices is critical.

Background The impact of lead from toxic waste sites on children in low and middle income countries has not been calculated due to a lack of exposure data. We sought to calculate this impact in Disability Adjusted Life Years (DALYs). Materials and methods Using an Integrated Exposure Uptake Biokinetic (IEUBK) model, we converted soil and drinking water lead levels from sites in the Blacksmith Institute׳s Toxic Sites Identification Program (TSIP) into mean blood lead levels (BLLs). We then calculated the incidence of mild mental retardation (MMR) and DALYs resulting from these BLLs. Results The TSIP included 200 sites in 31 countries with soil ( n =132) or drinking water ( n =68) lead levels, representing 779,989 children younger than 4 years of age potentially exposed to lead. Environmental lead levels produced a range of BLLs from 1.56 to 104.71 µg/dL. These BLLs equated to an estimated loss of 5.41–8.23 IQ points, resulting in an incidence of MMR of 6.03 per 1000 population and 76.1 DALYs per 1000 population. Discussion Soil and water lead levels at toxic waste sites predict BLLs that lower the intelligence quotient (IQ), with the resulting MMR potentially limiting individual- and country-level development. The preventable burden of disease produced by these sites highlights the need for toxic waste sites to be systematically identified, evaluated, and remediated.

Background In the United States, typhoid fever is rare. About 300 typhoid cases are reported to CDC annually through the National Typhoid and Paratyphoid Fever Surveillance (NTPFS) system. Most are acquired during international travel and while visiting friends and relatives. CDC recommends pretravel vaccination of at-risk children with one of two currently available vaccines: oral (age ≥6 years) or injectable (age ≥2 years). In anticipation of licensure of new protein-conjugate typhoid vaccines that could be administered to children ≥6 months old, we characterized clinical, epidemiologic, and antimicrobial resistance data of pediatric typhoid fever cases reported to CDC. Methods We reviewed laboratory-confirmed Salmonella enterica serotype Typhi infections reported to NTPFS and antimicrobial resistance data on Typhi isolates in the National Antimicrobial Resistance Monitoring System (NARMS) from 1999 to 2015. Results Of 2,051 pediatric (≤18 years) cases of typhoid fever, 80% had traveled internationally within 30 days of illness onset (most frequently to South Asia [82%]), 81% were hospitalized (median duration 6 days; range 0–77 days), and none died. Eight hundred twenty-seven (40%) were Conclusion Among pediatric cases of typhoid fever, 94% of currently vaccine-eligible travelers were unvaccinated. Emphasis on current vaccine indications and an effective pretravel typhoid vaccine for children between 6 months and 2 years old available during routine immunization visits could begin to reduce the burden of disease, and help prevent drug-resistant infections, in this vulnerable age group. Disclosures All authors: No reported disclosures.

Dietary supplements are increasingly marketed to and consumed by the American public for a variety of purported health benefits. On 9 September 2013, the Hawaii Department of Health (HDOH) was notified of a cluster of acute hepatitis and fulminant hepatic failure among individuals with exposure to the dietary supplement OxyELITE Pro™ (OEP). HDOH conducted an outbreak investigation in collaboration with federal partners. Physicians were asked to report cases, defined as individuals with acute onset hepatitis of unknown etiology on or after 1 April 2013, a history of weight-loss/muscle-building dietary supplement use during the 60 days before illness onset, and residence in Hawaii during the period of exposure. Reported cases' medical records were reviewed, questionnaires were administered, and a product investigation, including chemical analyses and traceback, was conducted. Of 76 reports, 44 (58%) met case definition; of these, 36 (82%) reported OEP exposure during the two months before illness. No other common supplements or exposures were observed. Within the OEP-exposed subset, two patients required liver transplantation, and a third patient died. Excessive product dosing was not reported. No unique lot numbers were identified; there were multiple mainland distribution points, and lot numbers common to cases in Hawaii were also identified in continental states. Product analysis found consumed products were consistent with labeled ingredients; the mechanism of hepatotoxicity was not identified. We report one of the largest statewide outbreaks of dietary supplement-associated hepatotoxicity. The implicated product was OEP. The increasing popularity of dietary supplements raises the potential for additional clusters of dietary supplement-related adverse events. Copyright © 2015 John Wiley & Sons, Ltd.

Background Salmonella Typhi (Typhi) causes typhoid fever, accounting for an estimated 5,700 illnesses and 623 hospitalizations per year in the United States. Most infections are acquired during travel to regions outside the United States where typhoid fever is prevalent and antimicrobial resistance is a problem. Fluoroquinolones (e.g., ciprofloxacin) are considered the treatment of choice for susceptible Typhi infections due to their superior ability to concentrate intracellularly and in bile, however, nonsusceptibility has been associated with treatment failure or delayed response. Azithromycin and ceftriaxone are treatment options. We describe antimicrobial susceptibility among Typhi isolates in the United States and the implications for management. Methods The National Antimicrobial Resistance Monitoring System at CDC conducts susceptibility testing on all Typhi isolates submitted by public health laboratories. We used broth microdilution to determine minimum inhibitory concentrations (MICs) to agents representing 9 antimicrobial classes and categorized isolates according to criteria from the Clinical and Laboratory Standards Institute. We defined ciprofloxacin nonsusceptibility as MIC ≥0.12 μg/mL, ciprofloxacin resistance as MIC ≥1, azithromycin resistance as MIC ≥32, and ceftriaxone resistance as MIC ≥4. Results From 2003–2015, isolates were tested from 4,550 patients; 2,760 (61%) were ciprofloxacin nonsusceptible, 4% were ciprofloxacin resistant. One isolate was azithromycin resistant and none were ceftriaxone resistant. Ciprofloxacin nonsusceptibility increased from 39% in 2003 to 66% in 2015; resistance increased from 0.3% to 8%. Median age of patients was 23 years (range 1–99 years), 53% were male, most were from the Northeast (33%) or the West (29%), and 74% had an isolate from blood. Conclusion Two thirds of Typhi isolates exhibited ciprofloxacin nonsusceptibility, which has increased over the last decade, and full resistance is increasing. Clinicians should be aware of high rates of fluoroquinolone nonsusceptibility when selecting empiric therapy and should tailor antimicrobial treatment to susceptibility results when feasible. Azithromycin and ceftriaxone remain important treatment options. Disclosures All authors: No reported disclosures.

On April 2, 2015, four patients were evaluated at the University of Mississippi Medical Center (UMMC) in Jackson, Mississippi, for agitated delirium after using synthetic cannabinoids. Over the next 3 days, 24 additional persons went to UMMC with illnesses suspected to be related to synthetic cannabinoid use; one patient died. UMMC notified the Mississippi State Department of Health, which issued a statewide alert via the Health Alert Network on April 5, requesting that health care providers report suspected cases of synthetic cannabinoid intoxication to the Mississippi Poison Control Center (MPCC). A suspected case was defined as the occurrence of at least two of the following symptoms: sweating, severe agitation, or psychosis in a person with known or suspected synthetic cannabinoid use. A second statewide alert was issued on April 13, instructing all Mississippi emergency departments to submit line lists of suspected patients to MPCC each day. By April 21, 16 days after the first alert was issued, MPCC had received reports of approximately 400 cases, including eight deaths possibly linked to synthetic cannabinoid use; in contrast, during April 2012–March 2015, the median number of telephone calls to MPCC regarding synthetic cannabinoid use was one per month (range = 0–11). The Mississippi State Department of Health, with the assistance of CDC, initiated an investigation to better characterize the outbreak, identify risk factors associated with severe illness, and prevent additional illnesses and deaths.

Background: Prior calculations of the burden of disease from toxic exposures have not included estimates of the burden from toxic waste sites due to the absence of exposure data. Objective: We developed a disability-adjusted life year (DALY)-based estimate of the disease burden attributable to toxic waste sites. We focused on three low- and middle-income countries (LMICs): India, Indonesia, and the Philippines. Methods: Sites were identified through the Blacksmith Institute’s Toxic Sites Identification Program, a global effort to identify waste sites in LMICs. At least one of eight toxic chemicals was sampled in environmental media at each site, and the population at risk estimated. By combining estimates of disease incidence from these exposures with population data, we calculated the DALYs attributable to exposures at each site. Results: We estimated that in 2010, 8,629,750 persons were at risk of exposure to industrial pollutants at 373 toxic waste sites in the three countries, and that these exposures resulted in 828,722 DALYs, with a range of 814,934–1,557,121 DALYs, depending on the weighting factor used. This disease burden is comparable to estimated burdens for outdoor air pollution (1,448,612 DALYs) and malaria (725,000 DALYs) in these countries. Lead and hexavalent chromium collectively accounted for 99.2% of the total DALYs for the chemicals evaluated. Conclusions: Toxic waste sites are responsible for a significant burden of disease in LMICs. Although some factors, such as unidentified and unscreened sites, may cause our estimate to be an underestimate of the actual burden of disease, other factors, such as extrapolation of environmental sampling to the entire exposed population, may result in an overestimate of the burden of disease attributable to these sites. Toxic waste sites are a major, and heretofore underrecognized, global health problem.

Identification and systematic assessment of hazardous wastes sites in low and middle-income countries has lagged. Hazardous waste problems are especially severe in lower income Asian countries where environmental regulations are non-existent, nonspecific or poorly enforced. In these countries extensive unregulated industrial development has created waste sites in densely populated urban areas. These sites appear to pose significant risks to public health, and especially to the health of children. To assess potential health risks from chemical contamination at hazardous waste sites in Asia, we assessed 679 sites. A total of 169 sites in 7 countries were classified as contaminated by lead. Eighty-two of these sites contained lead at levels high enough to produce elevated blood lead levels in surrounding populations. To estimate the burden of pediatric lead poisoning associated with exposure to lead in soil and water at these 82 lead-contaminated sites, we used standard toxicokinetic models that relate levels of lead in soil and water to blood lead levels in children. We calculated blood lead levels, and we quantified losses of intelligence (reductions in IQ scores) that were attributable to lead exposure at these sites. We found that 189,725 children in the 7 countries are at risk of diminished intelligence as a consequence of exposure to elevated levels of lead in water and soil at hazardous waste sites. Depending on choice of model, these decrements ranged from 4.94 to 14.96 IQ points. Given the restricted scope of this survey and the conservative estimation procedures employed, this number is almost certainly an underestimate of the full burden of disease. Exposure to toxic chemicals from hazardous waste sites is an important and heretofore insufficiently examined contributor to the Global Burden of Disease.