A review of the evidence to support interim reference level for dietary lead exposure in adults.

FDA developed the interim reference level (IRL) for lead of 3 µg/day in children and 12.5 µg/day in women of childbearing age (WOCBA) to better protect the fetus from lead toxicity. These IRLs correspond to a blood lead level (BLL) of 0.5 µg/dL in both populations. The current investigation was performed to determine if the IRL for WOCBA should apply to the general population of adults. A literature review of epidemiological studies was conducted to determine whether a BLL of 0.5 µg/dL is associated with adverse effects in adults. Some studies reported adverse effects over a wide range of BLLs that included 0.5 µg/dL adding uncertainty to conclusions about effects at 0.5 µg/dL; however, no studies clearly identified this BLL as an adverse effect level. Results also showed that the previously developed PTTDI for adults of 75 µg/day lead may not be health protective, supporting use of a lower reference value for lead toxicity in this population group. Use of the 12.5 µg/day IRL as a benchmark for dietary lead intake is one way FDA will ensure that dietary lead intake in adults is reduced.

U.S. Food and Drug Administration's interim reference levels for dietary lead exposure in children and women of childbearing age.

Reducing lead exposure is a public health priority for the US Food and Drug Administration as well as other federal agencies. The goals of this research were to 1) update the maximum daily dietary intake of lead from food, termed an interim reference level (IRL), for children and for women of childbearing age (WOCBA) and 2) to confirm through a literature review that with the exception of neurodevelopment, which was not evaluated here, no adverse effects of lead consistently occur at the blood lead level (BLL) associated with the IRL. Because no safe level of lead exposure has yet been identified for children's health, the IRLs of 3 µg/day for children and 12.5 µg/day for WOCBA were derived from the Centers for Disease Control and Prevention reference value of 5 µg/dL BLL, the level at which public health actions should be initiated. The literature review showed that no adverse effects of lead consistently occurred at the BLL associated with the IRLs (0.5 µg/dL). The IRLs of 3 µg/day for children and 12.5 µg/day for WOCBA should serve as useful benchmarks in evaluating the potential for adverse effects of dietary lead.

The Role of Adverse Event Reporting in the FDA Response to a Multistate Outbreak of Liver Disease Associated with a Dietary Supplement.

OBJECTIVE: Liver disease is a potential complication from using dietary supplements. This study investigated an outbreak of non-viral liver disease associated with the use of OxyELITE Pro(TM), a dietary supplement used for weight loss and/or muscle building. METHODS: Illness details were ascertained from MedWatch reports submitted to the U.S. Food and Drug Administration (FDA) describing consumers who ingested OxyELITE Pro alone or in combination with other dietary supplements. FDA's Forensic Chemistry Center analyzed samples of OxyELITE Pro. RESULTS: From February 2012 to February 2014, FDA received 114 reports of adverse events of all kinds involving consumers who ingested OxyELITE Pro. The onset of illness for the first report was December 2010 and for the last report was January 2014. Thirty-three states, two foreign nations, and Puerto Rico submitted reports. Fifty-five of the reports (48%) described liver disease in the absence of viral infection, gallbladder disease, autoimmune disease, or other known causes of liver damage. A total of 33 (60%) of these patients were hospitalized, and three underwent liver transplantation. In early 2013, OxyELITE Pro products entered the market with a formulation distinct from products sold previously. The new formulation replaced 1,3-dimethylamylamine with aegeline. However, the manufacturer failed to submit to FDA a required "new dietary ingredient" notice for the use of aegeline in OxyELITE Pro products. Laboratory analysis identified no drugs, poisons, pharmaceuticals, toxic metals, usnic acid, N-Nitroso-fenfluramine, pyrrolizidine alkaloids, aristocholic acid, or phenethylamines in the products. CONCLUSIONS: Vigilant surveillance is required for adverse events linked to the use of dietary supplements.

Pandemic influenza planning, United States, 1978-2008.

During the past century, 4 influenza pandemics occurred. After the emergence of a novel influenza virus of swine origin in 1976, national, state, and local US public health authorities began planning efforts to respond to future pandemics. Several events have since stimulated progress in public health emergency planning: the 1997 avian influenza A(H5N1) outbreak in Hong Kong, China; the 2001 anthrax attacks in the United States; the 2003 outbreak of severe acute respiratory syndrome; and the 2003 reemergence of influenza A(H5N1) virus infection in humans. We outline the evolution of US pandemic planning since the late 1970s, summarize planning accomplishments, and explain their ongoing importance. The public health community's response to the 2009 influenza A(H1N1)pdm09 pandemic demonstrated the value of planning and provided insights into improving future plans and response efforts. Preparedness planning will enhance the collective, multilevel response to future public health crises.

Arsenic poisoning caused by intentional contamination of coffee at a church gathering--an epidemiological approach to a forensic investigation.

An outbreak of apparent food-borne illness following a church gathering was promptly reported to the Maine Bureau of Health. Gastrointestinal symptoms among church attendees were initially attributed to consumption of leftover sandwiches that had been served the previous day. However, a rapid epidemiological and laboratory assessment revealed the etiology of illness, including the death of an elderly gentleman, was not food-borne in origin. A criminal investigation determined that deliberate arsenic contamination of the brewed coffee by one of the church members was the source of the outbreak. Public health officials and criminal investigators must be aware that intentional biologic aggression can initially present as typical unintentional disease outbreaks. Practitioners must also consider the need to properly maintain and preserve potential forensic evidence. This case demonstrates the key role public health practitioners may play in criminal investigations.

Pandemic influenza: implications for programs controlling for HIV infection, tuberculosis, and chronic viral hepatitis.

Among vulnerable populations during an influenza pandemic are persons with or at risk for HIV infection, tuberculosis, or chronic viral hepatitis. HIV-infected persons have higher rates of hospitalization, prolonged illness, and increased mortality from influenza compared with the general population. Persons with tuberculosis and chronic viral hepatitis may also be at increased risk of morbidity and mortality from influenza because of altered immunity and chronic illness. These populations also face social and structural barriers that will be exacerbated by a pandemic. Existing infrastructure should be expanded and pandemic planning should include preparations to reduce the risks for these populations.

Increased recognition of Powassan encephalitis in the United States, 1999-2005.

Powassan virus (POWV) disease is a rare human disease caused by a tick-borne encephalitis group flavivirus maintained in a transmission cycle between Ixodes cookei and other ixodid ticks and small and medium-sized mammals. During 1958-1998, only 27 POWV disease cases (mostly Powassan encephalitis) were reported from eastern Canada and the northeastern United States (average, 0.7 cases per year). During 1999-2005, nine cases (described herein) of serologically confirmed POWV disease were reported in the United States (average, 1.3 cases per year): four from Maine, two from New York, and one each from Michigan, Vermont, and Wisconsin. The Michigan and Wisconsin cases are the first ever reported from the north-central United States. Of these nine patients, 5 (56%) were men, the median age was 69 years (range: 25-91 years), and 6 (67%) had onset during May-July. All but one patient developed encephalitis with acute onset of profound muscle weakness, confusion, and other severe neurologic signs. In one case, no neurologic symptoms were present but the presence of pleocytosis, an elevated cerebrospinal fluid (CSF) protein concentration, and POWV-specific immunoglobulin M in CSF suggested neuroinvasion. All patients recovered from their acute disease, but most had long-term neurologic sequelae. Periresidential ecologic investigations were performed in three cases, including tests of local mammals and ticks for evidence of POWV infection. Woodchucks (Marmota monax), striped skunks (Mephitis mephitis), and a raccoon (Procyon lotor) collected at two of the Maine case-patients' residences had neutralizing antibody titers to POWV. I. cookei were found on woodchucks and skunks and questing in grassy areas of one of these residences; all were negative for POWV. Although POWV disease is rare, it is probably under-recognized, and it causes significant morbidity, and thus is an additional tick-borne emerging infectious disease entity. Because no vaccine or specific therapy is available, the basis of prevention is personal protection from ticks (or "tick hygiene") and reduced exposure to peridomestic wild mammals.

Postexposure interventions to prevent infection with HBV, HCV, or HIV, and tetanus in people wounded during bombings and other mass casualty events--United States, 2008: recommendations of the Centers for Disease Control and Prevention and Disaster Medicine and Public Health Preparedness.

People wounded during bombings or other events resulting in mass casualties or in conjunction with the resulting emergency response may be exposed to blood, body fluids, or tissue from other injured people and thus be at risk for bloodborne infections such as hepatitis B virus, hepatitis C virus, human immunodeficiency virus, or tetanus. This report adapts existing general recommendations on the use of immunization and postexposure prophylaxis for tetanus and for occupational and nonoccupational exposures to bloodborne pathogens to the specific situation of a mass casualty event. Decisions regarding the implementation of prophylaxis are complex, and drawing parallels from existing guidelines is difficult. For any prophylactic intervention to be implemented effectively, guidance must be simple, straightforward, and logistically undemanding. Critical review during development of this guidance was provided by representatives of the National Association of County and City Health Officials, the Council of State and Territorial Epidemiologists, and representatives of the acute injury care, trauma, and emergency response medical communities participating in the Centers for Disease Control and Prevention's Terrorism Injuries: Information, Dissemination and Exchange project. There recommendations contained in this report represent the consensus of US federal public health officials and reflect the experience and input of public health officials at all levels of government and the acute injury response community.

Recommendations for postexposure interventions to prevent infection with hepatitis B virus, hepatitis C virus, or human immunodeficiency virus, and tetanus in persons wounded during bombings and other mass-casualty events--United States, 2008: recommendations of the Centers for Disease Control and Prevention (CDC).

This report outlines recommendations for postexposure interventions to prevent infection with hepatitis B virus, hepatitis C virus, or human immunodeficiency virus, and tetanus in persons wounded during bombings or other events resulting in mass casualties. Persons wounded during such events or in conjunction with the resulting emergency response might be exposed to blood, body fluids, or tissue from other injured persons and thus be at risk for bloodborne infections. This report adapts existing general recommendations on the use of immunization and postexposure prophylaxis for tetanus and for occupational and nonoccupational exposures to bloodborne pathogens to the specific situation of a mass-casualty event. Decisions regarding the implementation of prophylaxis are complex, and drawing parallels from existing guidelines is difficult. For any prophylactic intervention to be implemented effectively, guidance must be simple, straightforward, and logistically undemanding. Critical review during development of this guidance was provided by representatives of the National Association of County and City Health Officials, the Council of State and Territorial Epidemiologists, and representatives of the acute injury care, trauma and emergency response medical communities participating in CDC's Terrorism Injuries: Information, Dissemination and Exchange (TIIDE) project. The recommendations contained in this report represent the consensus of U.S. federal public health officials and reflect the experience and input of public health officials at all levels of government and the acute injury response community.

Risk of infections associated with improperly reprocessed transrectal ultrasound-guided prostate biopsy equipment.

OBJECTIVE: A hospital discovered a lapse in the reprocessing procedures for transrectal ultrasound-guided prostate biopsy equipment. An investigation was initiated to assess the risks of transmission of hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV), and bacteria during prostate biopsies. METHODS: We offered testing for HBV, HCV, and HIV infection to patients who had undergone prostate biopsies from January 30, 2003, through January 27, 2006. We reviewed their medical records and obtained information on the reprocessing procedures that were in use at the time for the prostate biopsy equipment. SETTING: A healthcare facility in Maine. RESULTS: Of the 528 patients exposed to improperly reprocessed prostate biopsy equipment, none tested positive for HIV or HCV. Sixteen patients (3%) tested positive for past HBV infection but had no prebiopsy HBV serologic test results available (ie, transmission from improperly reprocessed biopsy equipment was possible), and 11 (2%) had evidence of postbiopsy bacterial infections. The number of cases of HBV and bacterial infections were within reported ranges for this population and were not clustered in time. Review of the reprocessing procedures in use at the time revealed that the manufacturer-recommended brushes for cleaning the reusable biopsy needle guide were never used. Brushes did not come with the equipment and had to be ordered separately. CONCLUSIONS: Despite the lack of evidence of pathogen transmission in this investigation, it is critical to review the manufacturer's reprocessing recommendations and to establish appropriate procedures to avert potential pathogen transmission and subsequent patient concerns. This investigation provides a better understanding of the risks associated with improperly reprocessed transrectal ultrasound prostate biopsy equipment and serves as a methodologic tool for future investigations.

Challenges to implementing second-dose varicella vaccination during an outbreak in the absence of a routine 2-dose vaccination requirement--Maine, 2006.

In June 2005, the Advisory Committee on Immunization Practices (ACIP) recommended administering a second dose of varicella vaccine during outbreaks, supplementing the routine 1-dose requirement. From October 2005 to January 2006, a varicella outbreak occurred in Maine in a highly vaccinated elementary school population. We investigated the outbreak, held a school-based vaccination clinic, and assessed costs in implementing ACIP's outbreak-response recommendation. Parents completed questionnaires and case investigation interviews. Personnel at the Maine Center for Disease Control and Prevention, the school in which the outbreak occurred ("school A"), and physician offices completed economic surveys. Forty-eight cases occurred, with no hospitalizations or deaths. Vaccine effectiveness was 86.6% (95% confidence interval, 82.0%-90.1%). Of 240 eligible students, 132 (55.0%) received second-dose vaccination. Implementing ACIP's outbreak-response recommendation was challenging and cost approximately $26,875. Additionally, the routine 1-dose varicella vaccination policy did not confer adequate population immunity to prevent this outbreak. These findings support ACIP's June 2007 recommendation for a routine 2-dose varicella vaccination program.

A hospital outbreak of diarrhea due to an emerging epidemic strain of Clostridium difficile.

BACKGROUND: Increased Clostridium difficile-associated disease (CDAD) in a hospital and an affiliated long-term care facility continued despite infection control measures. We investigated this outbreak to determine risk factors and transmission settings. METHODS: The CDAD cases were compared according to where the disease was likely acquired based on health care exposure and characterization of isolates from case patients, asymptomatic carriers, and the environment. Antimicrobial susceptibility testing, strain typing using pulsed-field gel electrophoresis, and toxinotyping were performed, and toxins A and B, binary toxin, and deletions in the tcdC gene were detected using polymerase chain reaction. Risk factors were examined in a case-control study, and overall antimicrobial use was compared at the hospital before and during the outbreak. RESULTS: Significant increases were observed in hospital-acquired (0.19 vs 0.86; P < .001) and long-term care facility-acquired (0.04 vs 0.31; P = .004) CDAD cases per 100 admissions as a result of transmission of a toxinotype III strain at the hospital and a toxinotype 0 strain at the long-term care facility. The toxinotype III strain was positive for binary toxin, an 18-base pair deletion in tcdC, and increased resistance to fluoroquinolones. Independent risk factors for CDAD included use of fluoroquinolones (odds ratio [OR], 3.22; P = .04), cephalosporins (OR, 5.19; P = .006), and proton pump inhibitors (OR, 5.02; P = .02). A significant increase in fluoroquinolone use at the hospital took place during the outbreak (185.5 defined daily doses per 1000 patient-days vs 200.9 defined daily doses per 1000 patient-days; P < .001). CONCLUSIONS: The hospital outbreak of CDAD was caused by transmission of a more virulent, fluoroquinolone-resistant strain of C difficile. More selective fluoroquinolone and proton pump inhibitor use may be important in controlling and preventing such outbreaks.

Outbreak of multidrug-resistant Salmonella enterica serotype Typhimurium Definitive Type 104 infection linked to commercial ground beef, northeastern United States, 2003-2004.

BACKGROUND: Multidrug-resistant Salmonella enterica serotype Typhimurium Definitive Type 104 (DT104) emerged in the 1990s and is associated with greater clinical severity than pansusceptible S. Typhimurium. Although infection with DT104 is common in the United States, it is rarely associated with outbreaks. From October to December 2003, a cluster of DT104 infections with indistinguishable pulsed-field gel electrophoresis patterns was identified in the northeastern United States. METHODS: A case-control study that assessed exposures compared case patients to age- and geography-matched control subjects. Information on consumer purchasing and grocery store suppliers was used to trace the implicated food to its source. RESULTS: We identified 58 case patients in 9 states by pulsed-field gel electrophoresis. Representative isolates were phage type DT104 and were resistant to ampicillin, chloramphenicol, streptomycin, sulfamethoxazole, and tetracycline (R-type ACSSuT). Of 27 patients interviewed for the case-control study, 41% were hospitalized (median duration of hospitalization, 4 days). Compared with 71 healthy control subjects, case patients had more medical comorbidities (matched odds ratio, 4.3; 95% confidence interval, 1.5-12.7). Illness was associated with consuming store-bought ground beef prepared as hamburgers at home (matched odds ratio, 5.3; 95% confidence interval, 1.9-15.3) and with eating raw ground beef (P< or =.001). Seven case patients (27%), but no control subjects, ate raw ground beef. Product traceback linked cases to a single large ground beef manufacturer previously implicated in a multistate outbreak of highly drug-resistant Salmonella enterica Newport infections in 2002. CONCLUSIONS: This first multistate outbreak of highly drug-resistant S. Typhimurium DT104 infection associated with ground beef highlights the need for enhanced animal health surveillance and infection control, prudent use of antimicrobials for animals, improved pathogen reduction during processing, and better product tracking and consumer education.

Importance of catch-up vaccination: experience from a varicella outbreak, Maine, 2002-2003.

OBJECTIVE: During December 2002 to January 2003, a varicella outbreak occurred in an elementary school in Maine. Just 1 month before detecting the outbreak, Maine implemented varicella vaccine requirements for child care but did not require vaccination for school entry. We investigated this outbreak to examine reasons for its occurrence, including vaccine failure. METHODS: A self-administered questionnaire was sent to all students' parents to determine student disease status, medical conditions, and vaccination status, which was further confirmed by review of medical records. Parental reporting of chickenpox/varicella that occurred since September 1, 2002, in a student who attended the school was used to define a case. Parents of cases were interviewed by telephone about disease characteristics. Disease severity was classified on the basis of the number of skin lesions and the occurrence of complications. Vaccine effectiveness was calculated by comparing varicella attack rates for any disease, for moderate to severe disease, and for severe disease among vaccinated and unvaccinated students. RESULTS: We obtained complete information for 296 (81%) of 364 students. Varicella vaccine coverage was 74% overall and decreased by grade, from 90% in kindergarten to 60% in third grade. Attack rates increased significantly from 14% in kindergarten to 37% in third grade. Of the 53 varicella cases, 36 (68%) were unvaccinated, 12 (22%) were vaccinated, and 5 (10%) had previous disease history. Vaccine effectiveness was 89% (95% confidence interval [CI]: 79-94%) against disease of any severity, 96% (95% CI: 88-99%) against moderate to severe disease, and 100% (95% CI: undefined) against severe disease. Twenty-two percent of unvaccinated students had severe disease and 1 was hospitalized for a skin infection, whereas none of the vaccinated cases reported severe disease. CONCLUSION: This outbreak was attributable primarily to failure to vaccinate, especially among children in grades 1 through 3. Catch-up vaccination of susceptible older children and adolescents is especially important to prevent accumulation of susceptibility in these groups, in which the natural disease is more severe. School entry requirements will contribute to a more rapid implementation of the existing recommendations for vaccination.

Preparing for pandemic influenza: the need for enhanced surveillance.

In the US, planning for the next influenza pandemic is occurring in parallel at the national, state and local levels. Certain issues, such as conducting surveillance and purchasing pandemic vaccine, require co-ordination at the national level. However, most prevention and control actions will be implemented at the state and local levels, which vary widely in terms of population demographics, culture (e.g. rural versus urban) and available resources. In 1995, a survey by the Council of State and Territorial Epidemiologists (CSTE) found that only 29 (59%) states perceived a need to develop a specific influenza pandemic plan for their jurisdiction. Since then, the process of developing state and local plans has gained considerable momentum. Integration of these efforts with the national planning process has been facilitated by: (1) the mutual involvement of state and federal staff in both processes; (2) the sharing of draft documents; (3) the ongoing occurrence of local and national co-ordinating meetings; (4) the provision of financial resources by the federal government. So far, approximately 12 states either have drafted or begun drafting a state and local influenza pandemic plan. One of the benefits of the collaborative planning process has been the development of new working relationships and partnerships among several agencies at the state, local and national levels. Such efforts will improve our collective ability to rapidly investigate and control other emerging or re-emerging public health threats in the 21st century, be it a bioterrorist event, pandemic influenza, or any other catastrophic health event.