Fentanyl-associated fatalities among illicit drug users in Wayne County, Michigan (July 2005-May 2006).

BACKGROUND: During the summer of 2005, multiple cities in the United States began to report outbreaks of fentanyl-associated fatalities among illicit drug users. The objectives of this study were to (1) determine if an outbreak of fentanyl-associated fatalities occurred in mid-2005 to mid-2006 and (2) to examine trends and compare features of fentanyl-contaminated heroin-associated fatalities (FHFs) with non-fentanyl, heroin-associated fatalities (NFHFs) among illicit drug users. METHODS: Baseline prevalence of fentanyl- and heroin-associated deaths was estimated from January to May 2005 based on recorded cause of death (determined by the medical examiner (ME)) using the Wayne County, MI, USA toxicology database. The database was then queried for both FHFs and NFHFs between July 1, 2005 and May 12, 2006. A FHF was defined as having fentanyl or norfentanyl (metabolite) detected in any postmortem biological sample and either (1) detection of heroin or its metabolite (6-acetylmorphine) and/or cocaine or its metabolite (benzoylecgonine) in a postmortem biological specimen or (2) confirmation of fentanyl abuse as the cause of death by the ME or a medical history available sufficient enough to exclude prescription fentanyl or other therapeutic opioid use. A NFHF was defined as detection of heroin, 6-acetylmorphine (heroin metabolite) or morphine in any postmortem biological specimen, heroin overdose listed as the cause of death by the ME, and absence of fentanyl detection on postmortem laboratory testing. Information was systematically collected, trended for each group and then compared between the two groups with regard to demographic, exposure, autopsy, and toxicology data. Logistic regression was performed using SAS v 9.1 examining the effects of age, gender, and marital status with fentanyl group status. RESULTS: Monthly prevalence of fentanyl-associated fatalities among illicit drug users increased from an average of two in early 2005 to a peak of 24 in May, 2006. In total, 101 FHFs and 90 NFHFs were analyzed. The median age of decedents was 46 and 45 years for the fentanyl and non-fentanyl groups, respectively. Fentanyl-contaminated heroin-associated fatalities (FHFs) were more likely to be female (p = 0.003). Women aged over 44 years (OR = 4.67;95 % CI = 1.29-16.96) and divorced/widowed women (OR = 14.18;95 % CI = 1.59-127.01) were more likely to be FHFs when compared to women aged less than 44 years and single, respectively. A significant interaction occurred between gender and age, and gender and marital status. Most FHFs had central (heart) blood samples available for fentanyl testing (n = 96; 95 %): fentanyl was detected in most (n = 91; 95 %). Of these, close to half had no detectable heroin (or 6-acetylmorphine) concentrations (n = 37; 40.7 %). About half of these samples had detectable cocaine concentrations (n = 20; 54 %). Median fentanyl concentration in central blood samples was 0.02 µg/ml (n = 91, range <0.002-0.051 µg/ml) and 0.02 µg/ml (n = 32, range <0.004-0.069 µg/ml) in peripheral blood samples. The geometric mean of the ratio of central to peripheral values was 2.10 (median C/P = 1.75). At autopsy, pulmonary edema was the most frequently encountered finding for both groups (77 %). CONCLUSION: Illicit drugs may contain undeclared ingredients that may increase the likelihood of fatality in users. Gender differences in fentanyl-related mortality may be modified by age and/or marital status. These findings may help inform public health and prevention activities if fatalities associated with fentanyl-contaminated illicit drugs reoccur.

Perchlorate exposure from infant formula and comparisons with the perchlorate reference dose.

Perchlorate exposure may be higher in infants compared with older persons, due to diet (infant formula) and body weight versus intake considerations. Our primary objective was to quantitatively assess perchlorate concentrations in commercially available powdered infant formulas (PIFs). Secondary objectives were: (1) to estimate exposure in infants under different dosing scenarios and compare them with the perchlorate reference dose (RfD); (2) estimate the perchlorate concentration in water used for preparing PIFs that would result in a dose exceeding the RfD; and (3) estimate iodine intakes from PIFs. We quantified perchlorate levels in three samples (different lot numbers) of reconstituted PIF (using perchlorate-free water) from commercial brands of PIF in each of the following categories: bovine milk-based with lactose, soy-based, bovine milk-based but lactose-free, and elemental (typically consisting of synthetic amino acids). Exposure modeling was conducted to determine whether the RfD might be exceeded in 48 dosing scenarios that were dependent on age, centile energy intake per unit of body weight, body weight percentile, and PIF perchlorate concentration. We obtained three different samples in each of the five brands of bovine- and soy-based PIF, three different samples in each of the three brands of lactose-free PIF, and three different samples in two brands of elemental PIF. The results were as follows: bovine milk-based with lactose (1.72 microg/l, range: 0.68-5.05); soy-based (0.21 microg/l, range: 0.10-0.44); lactose-free (0.27 microg/l, range: 0.03-0.93); and elemental (0.18 microg/l, range: 0.08-0.4). Bovine milk-based PIFs with lactose had a significantly higher concentration of perchlorate (P<0.05) compared with all. Perchlorate was a contaminant of all commercially available PIFs tested. Bovine milk-based PIFs with lactose had a significantly higher perchlorate concentration perchlorate than soy, lactose-free, and elemental PIFs. The perchlorate RfD may be exceeded when certain bovine milk-based PIFs are ingested and/or when PIFs are reconstituted with perchlorate-contaminated water.

Hypothermia and other cold-related morbidity emergency department visits: United States, 1995-2004.

OBJECTIVE: Although hypothermia is preventable, little has been published on its epidemiology. This study estimates the incidence of hypothermia and other cold-related morbidity emergency department (ED) visits in the United States. METHODS: We identified hypothermia and other cold-related morbidity ED visits from the 1995- 2004 National Hospital Ambulatory Medical Care Surveys using the International Classification of Diseases, Ninth Revision (991.6-991.9) or cause-of-injury E-codes (901.0-901.9 and 988.3). RESULTS: In the United States there were an estimated 15 574 (95% CI = 9 103-22 045) hypothermia and other cold-related morbidity ED visits during 1995 to 2004. Compared with other ED patients, those with hypothermia and other cold-related morbidity diagnoses were older (mean age 45 vs 36 years; P = .009) and were more likely to be uninsured (risk ratio [RR] = 2.44; 95% CI = 1.54-3.84). Hypothermia and other cold-related morbidity ED visits required more transfers to critical care units (RR = 6.73; 95% CI = 1.8-25.0) than did other ED visits. CONCLUSIONS: Hypothermia and other cold-related morbidity is a preventable resource-intensive condition that tends to affect the disadvantaged.

Public health investigation after the discovery of ricin in a South Carolina postal facility.

OBJECTIVES: In October 2003, a package containing ricin and a note threatening to poison water supplies was discovered in a South Carolina postal facility, becoming the first potential chemical terrorism event involving ricin in the United States. We examined the comprehensive public health investigation that followed and discuss the lessons learned from it. METHODS: An investigation consisting primarily of environmental sampling for ricin contamination, performance of health assessments on affected personnel, and local, regional, and national surveillance for ricin-associated illness. RESULTS: Laboratory analysis of 75 environmental sampling specimens revealed no ricin contamination. Health assessments of 36 affected employees were completed. Local surveillance initially identified 3 suspected cases, and national surveillance identified 399 outliers during the 2-week period after the incident. No confirmed cases of ricin-associated illness were identified. CONCLUSIONS: A multifaceted and multidisciplinary approach is required for an effective public health response to a chemical threat such as ricin. The results of all of the described activities were used to determine that the facility was safe to reopen and that no public health threat existed.

Risk factors for acute leukemia in children: a review.

Although overall incidence is rare, leukemia is the most common type of childhood cancer. It accounts for 30% of all cancers diagnosed in children younger than 15 years. Within this population, acute lymphocytic leukemia (ALL) occurs approximately five times more frequently than acute myelogenous leukemia (AML) and accounts for approximately 78% of all childhood leukemia diagnoses. Epidemiologic studies of acute leukemias in children have examined possible risk factors, including genetic, infectious, and environmental, in an attempt to determine etiology. Only one environmental risk factor (ionizing radiation) has been significantly linked to ALL or AML. Most environmental risk factors have been found to be weakly and inconsistently associated with either form of acute childhood leukemia. Our review focuses on the demographics of childhood leukemia and the risk factors that have been associated with the development of childhood ALL or AML. The environmental risk factors discussed include ionizing radiation, non-ionizing radiation, hydrocarbons, pesticides, alcohol use, cigarette smoking, and illicit drug use. Knowledge of these particular risk factors can be used to support measures to reduce potentially harmful exposures and decrease the risk of disease. We also review genetic and infectious risk factors and other variables, including maternal reproductive history and birth characteristics.

Investigating childhood leukemia in Churchill County, Nevada.

BACKGROUND: Sixteen children diagnosed with acute leukemia between 1997 and 2002 lived in Churchill County, Nevada, at the time of or before their illness. Considering the county population and statewide cancer rate, fewer than two cases would be expected. OBJECTIVES: In March 2001, the Centers for Disease Control and Prevention led federal, state, and local agencies in a cross-sectional, case-comparison study to determine if ongoing environmental exposures posed a health risk to residents and to compare levels of contaminants in environmental and biologic samples collected from participating families. METHODS: Surveys with more than 500 variables were administered to 205 people in 69 families. Blood, urine, and cheek cell samples were collected and analyzed for 139 chemicals, eight viral markers, and several genetic polymorphisms. Air, water, soil, and dust samples were collected from almost 80 homes to measure more than 200 chemicals. RESULTS: The scope of this cancer cluster investigation exceeded any previous study of pediatric leukemia. Nonetheless, no exposure consistent with leukemia risk was identified. Overall, tungsten and arsenic levels in urine and water samples were significantly higher than national comparison values; however, levels were similar among case and comparison groups. CONCLUSIONS: Although the cases in this cancer cluster may in fact have a common etiology, their small number and the length of time between diagnosis and our exposure assessment lessen the ability to find an association between leukemia and environmental exposures. Given the limitations of individual cancer cluster investigations, it may prove more efficient to pool laboratory and questionnaire data from similar leukemia clusters.

Recognition of illness associated with covert chemical releases.

Public health threats from intentional releases of chemicals into the environment (ie, chemical terrorism) are an increasing concern in the United States. Recent situations of deliberate contamination of food and beverages with chemicals highlight the need for health care providers and public health officials to be alert for adult and pediatric patients in their communities who have signs and symptoms consistent with chemical exposures. In an effort to increase knowledge of surveillance and preparedness for illness related to potential chemical releases, we provide guidance to health care providers and public health personnel for recognizing illnesses or patterns of illnesses that might be associated with the intentional, covert release of chemical agents. In this article, we will discuss 5 examples of outbreaks of illnesses after a covert chemical release, obstacles to recognition of these illnesses, clues (ie, epidemiological patterns and syndromic presentations) that might enhance the recognition of illnesses from a covert chemical release, and public health strategies to enhance the rapid identification of a chemical terrorism event.

Ackee fruit poisoning: an outbreak investigation in Haiti 2000-2001, and review of the literature.

The Centers for Disease Control and Prevention (CDC) provided technical assistance to the Ministry of Health of Haiti during an outbreak of over 100 cases of acute illness and death in the northern region of Haiti during a 4-month period beginning in November 2000. The epidemiologic, clinical, and laboratory findings in this investigation indicated the ingestion of unripe ackee fruit as the most likely cause of this outbreak. This report describes the CDC field investigation in Haiti and gives a brief overview of the current state of knowledge about ackee poisoning.

Early detection of illness associated with poisonings of public health significance.

Since September 11, 2001, concern about potential terrorist attacks has increased in the United States. To reduce morbidity and mortality from outbreaks of illness from the intentional release of chemical agents, we examine data from the Toxic Exposure Surveillance System (TESS). TESS, a national system for timely collection of reports from US poison control centers, can facilitate early recognition of outbreaks of illness from chemical exposures. TESS data can serve as proxy markers for a diagnosis and may provide early alerts to potential outbreaks of covert events. We use 3 categories of information from TESS to detect potential outbreaks, including call volume, clinical effect, and substance-specific data. Analysis of the data identifies aberrations by comparing the observed number of events with a threshold based on historical data. Using TESS, we have identified several events of potential public health significance, including an arsenic poisoning at a local church gathering in Maine, the TOPOFF 2 national preparedness exercise, and contaminated food and water during the northeastern US blackout. Integration of poison control centers into the public health network will enhance the detection and response to emerging chemical threats. Traditionally, emergency physicians and other health care providers have used poison control centers for management information; their reporting to these centers is crucial in poisoning surveillance efforts.

Strategies for recognizing acute chemical-associated foodborne illness.

The U.S. food supply is vulnerable to contamination with chemicals and toxins. Public health officials and clinicians may misdiagnose patients with acute chemical-associated foodborne illness (CAFI) due to unfamiliarity with chemical illness, increased familiarity with infectious foodborne illness, nonspecific presentation of most foodborne chemical poisoning, lack of readily available analytic methodologies to detect chemicals, and lack of education on how to develop a differential diagnosis for CAFI. This article will review the unique features of CAFI in the acute setting, address important questions to help differentiate CAFI from other foodborne illness, discuss laboratory features of CAFI, and provide health officials and clinicians with a clinical symptom-based approach to assist with proper identification and differentiation of acute CAFI.

Ricin poisoning: a comprehensive review.

CONTEXT: The recent discoveries of ricin, a deadly biologic toxin, at a South Carolina postal facility, a White House mail facility, and a US senator's office has raised concerns among public health officials, physicians, and citizens. Ricin is one of the most potent and lethal substances known, particularly when inhaled. The ease with which the native plant (Ricinus communis) can be obtained and the toxin extracted makes ricin an attractive weapon. OBJECTIVES: To summarize the literature on ricin poisoning and provide recommendations based on our best professional judgment for clinicians and public health officials that are faced with deliberate release of ricin into the environment. LITERATURE ACQUISITION: Using PubMed, we searched MEDLINE and OLDMEDLINE databases (January 1950-August 2005). The Chemical and Biological Information Analysis Center database was searched for historical and military literature related to ricin toxicity. Book chapters, unpublished reports, monographs, relevant news reports, and Web material were also reviewed to find nonindexed articles. RESULTS: Most literature on ricin poisoning involves castor bean ingestion and experimental animal research. Aerosol release of ricin into the environment or adulteration of food and beverages are pathways to exposure likely to be exploited. Symptoms after ingestion (onset within 12 hours) are nonspecific and may include nausea, vomiting, diarrhea, and abdominal pain and may progress to hypotension, liver failure, renal dysfunction, and death due to multiorgan failure or cardiovascular collapse. Inhalation (onset of symptoms is likely within 8 hours) of ricin is expected to produce cough, dyspnea, arthralgias, and fever and may progress to respiratory distress and death, with few other organ system manifestations. Biological analytic methods for detecting ricin exposure are undergoing investigation and may soon be available through reference laboratories. Testing of environmental samples is available through federal reference laboratories. Currently, no antidote, vaccine, or other specific effective therapy is available for ricin poisoning or prevention. Prompt treatment with supportive care is necessary to limit morbidity and mortality. CONCLUSION: Health care workers and public health officials should consider ricin poisoning in patients with gastrointestinal or respiratory tract illness in the setting a credible threat. Poison control centers and public health authorities should be notified of any known illness associated with ricin exposure.

Methylenedioxymethamphetamine (ecstasy)-related hyperthermia.

MDMA (or 3, 4 methylenedioxymethamphetamine) was first manufactured in the 1920s and found to have structural similarities to both mescaline and amphetamines. Used briefly by some therapists in the 1970s and early 1980s as an adjunct to psychotherapy, it is now primarily abused by teenagers and young adults as an illicit recreational drug known as "ecstasy." As its popularity has increased, so have the number of fatalities and adverse events related to its use. We report six patients suffering fatal or life-threatening hyperthermia after MDMA use. These cases illustrate that hyperthermia associated with MDMA use cannot be solely attributed to rave parties (high ambient temperatures, excessive dancing, dehydration, and overcrowded conditions), drug contaminants, or co-ingestants. A better understanding of the etiology of hyperthermia after MDMA use is needed so that appropriate harm-reduction measures can be developed and instituted.

The Toxic Exposure Surveillance System (TESS): risk assessment and real-time toxicovigilance across United States poison centers.

The Toxic Exposure Surveillance System (TESS) is a uniform data set of US poison centers cases. Categories of information include the patient, the caller, the exposure, the substance(s), clinical toxicity, treatment, and medical outcome. The TESS database was initiated in 1985, and provides a baseline of more than 36.2 million cases through 2003. The database has been utilized for a number of safety evaluations. Consideration of the strengths and limitations of TESS data must be incorporated into data interpretation. Real-time toxicovigilance was initiated in 2003 with continuous uploading of new cases from all poison centers to a central database. Real-time toxicovigilance utilizing general and specific approaches is systematically run against TESS, further increasing the potential utility of poison center experiences as a means of early identification of potential public health threats.

Methylenedioxymethamphetamine (ecstasy)-related myocardial hypertrophy: an autopsy study.

BACKGROUND: Myocardial hypertrophy is a well-recognized complication of cocaine and methamphetamine abuse and is a strong, independent risk factor for sudden death, myocardial infarction, and congestive heart failure. We sought to determine if use of MDMA (methylenedioxyamphetamine or "ecstasy") is associated with myocardial hypertrophy at death. METHODS AND RESULTS: A matched, retrospective study using medical examiner (ME) death reports. Consecutive MDMA positive (+) and MDMA negative (-) deaths identified from MEs in 10 states and a local county, respectively. Five MDMA(-) cases were matched to each MDMA(+) case for age, sex, and ethnicity. MDMA(+) cases were confirmed using GC/MS and other drugs of abuse (e.g., cocaine and methamphetamine) were absent. Matched MDMA(-) cases were trauma fatalities with intact hearts and blood negative for all illicit stimulants. Cardiac weights were compared between the two groups. Twenty seven MDMA(+) deaths and 135 matched MDMA(-) deaths were enrolled. Mean age was 20 years (range 16--33 years); 44% were female. 70.4% were Caucasian, 14.8% African-American, 11.1% Asian, and 3.7% Hispanic. Mean heart weight of MDMA(+) fatalities was 315.7 and 277.2g for MDMA(-) fatalities (Diff=38.5 g; 95% CI=18.3--8.7). Multivariate analysis revealed that MDMA(+) fatalities were more likely to have an enlarged heart (OR=18.3; 95% CI=3.6--1.6). CONCLUSION: The findings of this study suggest that MDMA users might also be at risk for myocardial hypertrophy and possible cardiac toxicity, similar to other stimulants.

Tetramethylenedisulfotetramine: old agent and new terror.

Tetramethylenedisulfotetramine has accounted for numerous intentional and unintentional poisonings in China. In May 2002, the first known case of human illness in the United States caused by tetramethylenedisulfotetramine, a banned neurotoxic rodenticide from China, occurred in New York City. The clinical presentation after tetramethylenedisulfotetramine exposure is dose dependent, and the most recognized complication is status epilepticus. Poisonings may be fatal within hours. No known antidote exists, and treatment is mainly supportive. Anecdotal reports, case reports, and 2 animal studies suggest possible success with certain pharmacologic interventions, including pyridoxine and chelation therapy. Pesticide and rodenticide poisonings, whether intentional or unintentional, pose a serious threat to populations, and the availability of a banned rodenticide such as tetramethylenedisulfotetramine, with its associated morbidity and lethality, is a serious public health concern. Given the recent case report that confirms the presence of tetramethylenedisulfotetramine in the United States, the toxicity of the compound, its unique physical properties, the absence of an antidote, and the history of its use as an agent of intentional mass poisoning, public health entities have undertaken educational efforts to inform the public, health care providers, and emergency personnel of this potentially lethal rodenticide.

Case definitions for chemical poisoning.

When human illness results from an unintentional or intentional release of a toxin (chemicals produced by metabolism in an organism [e.g., ricin]) or a toxicant (natural or synthetic chemicals not metabolically produced by an organism [e.g., nerve agents]) into the environment, uniform reporting is necessary to direct appropriate resources, assess the extent of morbidity and mortality, track poisoned persons, and monitor response to intervention. In this report, CDC presents case definitions to facilitate uniform reporting among local, state, and federal public health agencies of illness resulting from a chemical release. The report also explains the rationale for the structure of the case definitions, the audience for whom it is intended, the setting in which the case definitions might be used, and reasons each chemical presented in the report was selected. Clinical knowledge and diagnostic tools (e.g., biologic laboratory tests) for detecting chemical poisoning are likely to improve over time. CDC will create new case definitions and revise existing definitions to meet the needs related to emerging threats and to enhance case definition sensitivity and specificity, when possible, with developing clinical information.

Methanol toxicity in a newborn.

BACKGROUND: Methanol poisoning during human pregnancy rarely has been described. We report the first human newborn with a documented methanol concentration resulting from maternal exposure. CASE REPORT: A 28-year-old pregnant woman EGA 30 weeks with HIV infection and asthma presented to the emergency department in respiratory distress. She was acidotic (pH 7.17) with an anion gap of 26, and fetal bradycardia was noted. Her son was delivered by emergent C-section (birthweight 950 g, Apgars 1 and 3) and required aggressive resuscitation. During his hospital course, acidosis (initial pH 6.9) persisted despite fluid, blood, and bicarbonate administration. His mother also had persistent metabolic acidosis despite fluids, bicarbonate, and dopamine. Results of other laboratory tests on the mother included undetectable ethanol and salicylates and an osmolar gap of 41. An ethanol drip was initiated for the mother 36 h after admission when a methanol level of 54 mg/dL was reported. When consulted on hospital day 3, our regional poison center recommended hemodialysis for the mother and administering fomepizole and testing the methanol level of the newborn (61.6 mg/dL). Because the infant developed a grade 4 intraventricular bleed, no further therapy was offered, and he died on day 4. His mother died on day 10. CONCLUSION: Fatal neonatal methanol toxicity can result from transplacental exposure.