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Background: The high mortality of systemic anthrax is likely a consequence of the severe central nervous system inflammation that occurs in anthrax meningitis. Effective treatment of such infections requires, at a minimum, adequate cerebrospinal fluid (CSF) antimicrobial concentrations., Methods: We reviewed English medical literature and regulatory documents to extract information on serum and CSF exposures for antimicrobials with in vitro activity against Bacillus anthracis. Using CSF pharmacokinetic exposures and in vitro B. anthracis susceptibility data, we used population pharmacokinetic modeling and Monte Carlo simulations to determine whether a specific antimicrobial dosage would likely achieve effective CSF antimicrobial activity in patients with normal to inflamed meninges (ie, an intact to markedly disrupted blood-brain barrier)., Results: The probability of microbiologic success at achievable antimicrobial dosages was high (≥95%) for ciprofloxacin, levofloxacin (500 mg every 12 hours), meropenem, imipenem/cilastatin, penicillin G, ampicillin, ampicillin/sulbactam, doxycycline, and minocycline; acceptable (90%-95%) for piperacillin/tazobactam and levofloxacin (750 mg every 24 hours); and low (<90%) for vancomycin, amikacin, clindamycin, and linezolid., Conclusions: Prompt empiric antimicrobial therapy of patients with suspected or confirmed anthrax meningitis may reduce the high morbidity and mortality. Our data support using several β-lactam-, fluoroquinolone-, and tetracycline-class antimicrobials as first-line and alternative agents for treatment of patients with anthrax meningitis; all should achieve effective microbiologic exposures. Our data suggest antimicrobials that should not be relied on to treat suspected or documented anthrax meningitis. Furthermore, the protein synthesis inhibitors clindamycin and linezolid can decrease toxin production and may be useful components of combination therapy., Competing Interests: Potential conflicts of interest . J. S. B. is supported by an NICHD grant (1 R01 HD095547-01). J. B. B. is supported by NIAID grants (R01 AI130185 and R01 AI136803). K. H., C. I., E. H., and P. Y. are career officers with the CDC. J. B. reports consulting fees from MicuRx Pharmaceuticals Inc, Aerovate Therapeutics, and Lupin and honorarium for a lecture under T32 (William Shafer, Emory) on antimicrobial pharmacology. A. W. K. reports stock from Pfizer, Johnson & Johnson, and AbbVie. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2024.)

Background: The Pediatric Acute Care Cardiology Collaborative (PAC3) is a learning network focused on improving acute care cardiology patient outcomes. Data submission timeliness is a vulnerability for PAC3 and most clinical registries, directly affecting collaborative benchmarking, quality improvement (QI) and research projects., Objective: PAC3 conducted a collaborative-wide QI project addressing data timeliness and efficiency. Data analysis of submitted cases from September 2019 to February 2020 revealed nine 'High Performer' centers who submitted cases within 67 days of hospital discharge (the limit for timeliness) >90% of the time and eight 'High Potential' sites who submitted timely cases <75% of the time. The primary aim was to increase case submission timeliness in 'High Potential' centers from 41% to 80% by December 2020. The secondary aim was to maintain timeliness in 'High Performer' sites., Method: During the intervention phase (March-December 2020), plan-do-study-act (PDSA) cycles included webinars, facilitated exploratory conversations, data review and development of a best practice guide ('Getting Started Toolkit'). On-boarded 'New Centers' starting in 2020 were also invited to test intervention effectiveness. Balancing measures included data collector job satisfaction and stress and resubmission rates., Results: 'High Performer' and 'High Potential' centers submitted 11 358 cases from November 2019 to December 2020. Timely submission rates for 'High Potential' centers improved from 40.6% to 74.6% and were maintained at >90% for 'High Performer' centers. 'New Centers' averaged 92.6% timely case submissions during their first 6 months. Data collector job satisfaction and stress were not impacted, and the resubmission rates did not increase., Conclusion: PAC3's multicenter QI project increased data submission timeliness in a large pediatric subspecialty registry. The lessons learned and the Toolkit developed can be applied in other registries to improve data submission efficiency, with resultant improvement in benchmarking, QI, research, length of stay and outcomes., (© The Author(s) 2022. Published by Oxford University Press on behalf of International Society for Quality in Health Care. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Anthrax is a toxin-mediated zoonotic disease caused by Bacillus anthracis, with a worldwide distribution recognized for millennia. Bacillus anthracis is considered a potential biowarfare agent., Methods: We completed a systematic review for clinical and demographic characteristics of adults and children hospitalized with anthrax (cutaneous, inhalation, ingestion, injection [from contaminated heroin], primary meningitis) abstracted from published case reports, case series, and line lists in English from 1880 through 2018, assessing treatment impact by type and severity of disease. We analyzed geographic distribution, route of infection, exposure to anthrax, and incubation period., Results: Data on 764 adults and 167 children were reviewed. Most cases reported for 1880 through 1915 were from Europe; those for 1916 through 1950 were from North America; and from 1951 on, cases were from Asia. Cutaneous was the most common form of anthrax for all populations. Since 1960, adult anthrax mortality has ranged from 31% for cutaneous to 90% for primary meningitis. Median incubation periods ranged from 1 day (interquartile range [IQR], 0-4) for injection to 7 days (IQR, 4-9) for inhalation anthrax. Most patients with inhalation anthrax developed pleural effusions and more than half with ingestion anthrax developed ascites. Treatment and critical care advances have improved survival for those with systemic symptoms, from approximately 30% in those untreated to approximately 70% in those receiving antimicrobials or antiserum/antitoxin., Conclusions: This review provides an improved evidence base for both clinical care of individual anthrax patients and public health planning for wide-area aerosol releases of B. anthracis spores., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2022. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Background: During an anthrax mass casualty event, prompt identification of patients with anthrax meningitis is important. Previous research has suggested use of a screening tool based on neurological symptoms and signs., Methods: Using historical anthrax patient data from 1880 through 2018, we analyzed risk factors for meningitis. We developed lists of symptoms and signs (ie, algorithms) for predicting meningitis with high sensitivity and specificity. We evaluated both single and paired algorithms as screening tools., Results: A single algorithm with 1 or more neurological symptoms or signs identifying patients with likely meningitis achieved high sensitivity (86%; 95% confidence interval [CI], 71%-100%) and specificity (90%; 95% CI, 82%-98%). Pairing algorithms with the same symptoms and signs (severe headache, altered mental status, meningeal signs, and "other neurological deficits") improved specificity (99%; 95% CI, 97%-100%) but left 17.3% of patients in a middle "indeterminate" meningitis category and in need of additional diagnostic testing to determine likely meningitis status. Pairing algorithms with differing symptoms and signs also improved specificity over the single algorithm (92%; 95% CI, 85%-99%) but categorized just 2.5% of patients as indeterminate., Conclusions: Our study confirms prior research suggesting quick and reliable assessment of patients for anthrax meningitis is possible based on the presence or absence of certain symptoms and signs. A single algorithm was adequate; however, if we assumed low-resource diagnostic testing was feasible for some patients, pairing algorithms improved specificity. Pairing algorithms with differing symptoms and signs minimized the proportion of patients requiring additional diagnostics., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2022.)

The neurological sequelae of Bacillus anthracis infection include a rapidly progressive fulminant meningoencephalitis frequently associated with intracranial hemorrhage, including subarachnoid and intracerebral hemorrhage. Higher mortality than other forms of bacterial meningitis suggests that antimicrobials and cardiopulmonary support alone may be insufficient and that strategies targeting the hemorrhage might improve outcomes. In this review, we describe the toxic role of intracranial hemorrhage in anthrax meningoencephalitis. We first examine the high incidence of intracranial hemorrhage in patients with anthrax meningoencephalitis. We then review common diseases that present with intracranial hemorrhage, including aneurysmal subarachnoid hemorrhage and spontaneous intracerebral hemorrhage, postulating applicability of established and potential neurointensive treatments to the multimodal management of hemorrhagic anthrax meningoencephalitis. Finally, we examine the therapeutic potential of minocycline, an antimicrobial that is effective against B. anthracis and that has been shown in preclinical studies to have neuroprotective properties, which thus might be repurposed for this historically fatal disease., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2022. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Bacillus anthracis has traditionally been considered the etiologic agent of anthrax. However, anthrax-like illness has been documented in welders and other metal workers infected with Bacillus cereus group spp. harboring pXO1 virulence genes that produce anthrax toxins. We present 2 recent cases of severe pneumonia in welders with B. cereus group infections and discuss potential risk factors for infection and treatment options, including antitoxin., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2022. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Background: Bacillus anthracis can cause anthrax and is a potential bioterrorism agent. The 2014 Centers for Disease Control and Prevention recommendations for medical countermeasures against anthrax were based on in vitro data and expert opinion. However, a century of previously uncompiled observational human data that often includes treatment and outcomes is available in the literature for analysis., Methods: We reviewed treatment outcomes for patients hospitalized with anthrax. We stratified patients by meningitis status, route of infection, and systemic criteria, then analyzed survival by treatment type, including antimicrobials, antitoxin/antiserum, and steroids. Using logistic regression, we calculated odds ratios and 95% confidence intervals to compare survival between treatments. We also calculated hospital length of stay. Finally, we evaluated antimicrobial postexposure prophylaxis (PEPAbx) using data from a 1970 Russian-language article., Results: We identified 965 anthrax patients reported from 1880 through 2018. After exclusions, 605 remained: 430 adults, 145 children, and 30 missing age. Survival was low for untreated patients and meningitis patients, regardless of treatment. Most patients with localized cutaneous or nonmeningitis systemic anthrax survived with 1 or more antimicrobials; patients with inhalation anthrax without meningitis fared better with at least 2. Bactericidal antimicrobials were effective for systemic anthrax; addition of a protein synthesis inhibitor(s) (PSI) to a bactericidal antimicrobial(s) did not improve survival. Likewise, addition of antitoxin/antiserum to antimicrobials did not improve survival. Mannitol improved survival for meningitis patients, but steroids did not. PEPAbx reduced risk of anthrax following exposure to B. anthracis., Conclusions: Combination therapy appeared to be superior to monotherapy for inhalation anthrax without meningitis. For anthrax meningitis, neither monotherapy nor combination therapy were particularly effective; however, numbers were small. For localized cutaneous anthrax, monotherapy was sufficient. For B. anthracis exposures, PEPAbx was effective., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2022. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Background: Cutaneous anthrax accounts for approximately 95% of anthrax cases worldwide. About 24% of untreated patients die, and many cases are complicated by meningitis. Here, we explore clinical features of cutaneous disease associated with poor outcomes., Methods: A systematic review identified 303 full-text articles published from 1950 through 2018 that met predefined inclusion criteria. Cases were abstracted, and descriptive analyses and univariate logistic regression were conducted to identify prognostic indicators for cutaneous anthrax., Results: Of 182 included patients, 47 (25.8%) died. Previously reported independent predictors for death or meningitis that we confirmed included fever or chills; nausea or vomiting; headache; severe headache; nonheadache, nonmeningeal signs; leukocytosis; and bacteremia. Newly identified predictors included anxiety, abdominal pain, diastolic hypotension, skin trauma, thoracic edema, malignant pustule edema, lymphadenopathy, and evidence of coagulopathy (all with P < .05)., Conclusions: We identified patient presentations not previously associated with poor outcomes., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2022. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Background: The deliberate use of Bacillus anthracis spores is believed by the US government to be a high bioweapons threat. The first line of defense following potential exposure to B. anthracis spores would be postexposure prophylaxis with antimicrobials that have activity against B. anthracis. Additional therapies to address the effects of toxins may be needed in systemically ill individuals. Over the last 2 decades, the United States government (USG) collaborated with the private sector to develop, test, and stockpile 3 antitoxins: anthrax immunoglobulin intravenous (AIGIV), raxibacumab, and obiltoxaximab. All 3 products target protective antigen, a protein factor common to the 2 exotoxins released by B. anthracis, and hamper or block the toxins' effects and prevent or reduce pathogenesis. These antitoxins were approved for licensure by the United States Food and Drug Administration based on animal efficacy studies compared to placebo., Methods: We describe USG-sponsored pre- and postlicensure studies that compared efficacy of 3 antitoxins in a New Zealand White rabbit model of inhalation anthrax; survival following a lethal aerosolized dose of B. anthracis spores was the key measure of effectiveness. To model therapeutic intervention, intravenous treatments were started following onset of antigenemia., Results: In pre- and postlicensure studies, all 3 antitoxins were superior to placebo; in the postlicensure study, raxibacumab and obiltoxaximab were superior to AIGIV, but neither was superior to the other., Conclusions: These data illustrate the relative therapeutic benefit of the 3 antitoxins and provide a rationale to prioritize their deployment., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2022. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Background: Anthrax is endemic to many countries, including the United States. The causative agent, Bacillus anthracis, poses a global bioterrorism threat. Without effective antimicrobial postexposure prophylaxis (PEPAbx) and treatment, the mortality of systemic anthrax is high. To inform clinical guidelines for PEPAbx and treatment of B. anthracis infections in humans, we systematically evaluated animal anthrax treatment model studies., Methods: We searched for survival outcome data in 9 scientific search engines for articles describing antimicrobial PEPAbx or treatment of anthrax in animals in any language through February 2019. We performed meta-analyses of efficacy of antimicrobial PEPAbx and treatment for each drug or drug combination using random-effects models. Pharmacokinetic/pharmacodynamic relationships were developed for 5 antimicrobials with available pharmacokinetic data. Monte Carlo simulations were used to predict unbound drug exposures in humans., Results: We synthesized data from 34 peer-reviewed studies with 3262 animals. For PEPAbx and treatment of infection by susceptible B. anthracis, effective monotherapy can be accomplished with fluoroquinolones, tetracyclines, β-lactams (including penicillin, amoxicillin-clavulanate, and imipenem-cilastatin), and lipopeptides or glycopeptides. For naturally occurring strains, unbound drug exposures in humans were predicted to adequately cover the minimal inhibitory concentrations (MICs; those required to inhibit the growth of 50% or 90% of organisms [MIC50 or MIC90]) for ciprofloxacin, levofloxacin, and doxycycline for both the PEPAbx and treatment targets. Dalbavancin covered its MIC50 for PEPAbx., Conclusions: These animal studies show many reviewed antimicrobials are good choices for PEPAbx or treatment of susceptible B. anthracis strains, and some are also promising options for combating resistant strains. Monte Carlo simulations suggest that oral ciprofloxacin, levofloxacin, and doxycycline are particularly robust choices for PEPAbx or treatment., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2022.)

Background: US Centers for Disease Control and Prevention guidelines currently recommend triple-therapy antimicrobial treatment for anthrax meningitis. In the Kyrgyz Republic, a country with endemic anthrax, cutaneous anthrax patients are routinely hospitalized and treated successfully with only monotherapy or dual therapy. Clinical algorithms have been developed to identify patients with likely anthrax meningitis based on signs and symptoms alone. We sought to retrospectively identify likely meningitis patients in the Kyrgyz Republic using a clinical algorithm and evaluate risk factors and their outcomes by type of treatment., Methods: We conducted a retrospective chart review of cutaneous anthrax patients in the Kyrgyz Republic from 2005 through 2012. Using previous methods, we developed a highly specific algorithm to categorize patients by meningitis status. We then evaluated patient risk factors, treatments, and outcomes by disease severity and meningitis status., Results: We categorized 37 of 230 cutaneous anthrax patients as likely having meningitis. All 37 likely meningitis patients survived, receiving only mono- or dual-therapy antimicrobials. We identified underlying medical conditions, such as obesity, hypertension, and chronic obstructive pulmonary disease, and tobacco and alcohol use, as potential risk factors for severe anthrax and anthrax meningitis., Conclusions: Based on our analyses, treatment of anthrax meningitis may not require 3 antimicrobials, which could impact future anthrax treatment recommendations. In addition, chronic comorbidities may increase risk for severe anthrax and anthrax meningitis. Future research should further investigate potential risk factors for severe anthrax and their impact on laboratory-confirmed meningitis and evaluate mono- and dual-therapy antimicrobial regimens for anthrax meningitis., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2022. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Bacillus anthracis, the causative agent of anthrax, is a high-consequence bacterial pathogen that occurs naturally in many parts of the world and is considered an agent of biowarfare or bioterrorism. Understanding antimicrobial susceptibility profiles of B. anthracis isolates is foundational to treating naturally occurring outbreaks and to public health preparedness in the event of an intentional release. In this systematic review, we searched the peer-reviewed literature for all publications detailing antimicrobial susceptibility testing of B. anthracis. Within the set of discovered articles, we collated a subset of publications detailing susceptibility testing that followed standardized protocols for Food and Drug Administration-approved, commercially available antimicrobials. We analyzed the findings from the discovered articles, including the reported minimal inhibitory concentrations. Across the literature, most B. anthracis isolates were reported as susceptible to current first-line antimicrobials recommended for postexposure prophylaxis and treatment. The data presented for potential alternative antimicrobials will be of use if significant resistance to first-line antimicrobials arises, the strain is bioengineered, or first-line antimicrobials are not tolerated or available., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2022. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Background: Bacillus anthracis, the causative agent of anthrax, is a potential bioterrorism agent. Anthrax meningitis is a common manifestation of B. anthracis infection, has high mortality, and requires more aggressive treatment than anthrax without meningitis. Its rapid identification and treatment are essential for successful management of an anthrax mass casualty incident., Methods: Three hundred six published reports from 1880 through 2013 met predefined inclusion criteria. We calculated descriptive statistics for abstracted cases and conducted multivariable regression on separate derivation and validation cohorts to identify clinical diagnostic and prognostic factors for anthrax meningitis., Results: One hundred thirty-two of 363 (36%) cases with systemic anthrax met anthrax meningitis criteria. Severe headache, altered mental status, meningeal signs, and other neurological signs at presentation independently predicted meningitis in the derivation cohort and were tested as a 4-item assessment tool for use during anthrax mass casualty incidents. Presence of any 1 factor on admission had a sensitivity for finding anthrax meningitis of 89% (83%) in the adult (pediatric) validation cohorts. Anthrax meningitis was unlikely in the absence of any of these signs or symptoms (likelihood ratio [LR]- = 0.12 [0.19] for adult [pediatric] cohorts), while presence of 2 or more made meningitis very likely (LR+ = 26.5 [30.0]). Survival of anthrax meningitis was predicted by treatment with a bactericidal agent (P = .005) and use of multiple antimicrobials (P = .01)., Conclusions: We developed an evidence-based assessment tool for screening patients for meningitis during an anthrax mass casualty incident. Its use could improve both patient outcomes and resource allocation in such an event., Competing Interests: None of the authors have any conflicts of interest. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the CDC., (Published by Oxford University Press for the Infectious Diseases Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Background: Randomized controlled trials testing the association between vitamin D status and upper respiratory tract infection (URTI) have given mixed results. During a multicenter, randomized controlled trial of colorectal adenoma chemoprevention, we tested whether 1000 IU/day vitamin D(3) supplementation reduced winter episodes and duration of URTI and its composite syndromes, influenza-like illness (ILI; fever and ≥2 of sore throat, cough, muscle ache, or headache) and colds (no fever, and ≥2 of runny nose, nasal congestion, sneezing, sore throat, cough, swollen or tender neck glands)., Methods: The 2259 trial participants were aged 45-75, in good health, had a history of colorectal adenoma, and had a serum 25-hydroxyvitamin D level ≥12 ng/mL. They were randomized to vitamin D(3) (1000 IU/day), calcium (1200 mg/day), both, or placebo. Of these, 759 participants completed daily symptom diaries. Secondary data included semiannual surveys of all participants., Results: Among those who completed symptom diaries, supplementation did not significantly reduce winter episodes of URTI (rate ratio [RR], 0.93; 95% confidence interval [CI], .79-1.09) including colds (RR, 0.93; 95% CI, .78-1.10) or ILI (RR, 0.95; 95% CI, .62-1.46), nor did it reduce winter days of illness (RR, 1.13; 95% CI, .90-1.43). There was no significant benefit according to adherence, influenza vaccination, body mass index, or baseline vitamin D status. Semiannual surveys of all participants (N = 2228) identified no benefit of supplementation on ILI (odds ratio [OR], 1.14; 95% CI, .84-1.54) or colds (OR, 1.03; 95% CI, .87-1.23)., Conclusions: Supplementation with 1000 IU/day vitamin D(3) did not significantly reduce the incidence or duration of URTI in adults with a baseline serum 25-hydroxyvitamin D level ≥12 ng/mL.

Rheumatoid arthritis (RA) is a systemic autoimmune disease with unknown etiology where tumor necrosis factor-α (TNFα) plays a critical role. Etanercept, a recombinant fusion protein of human soluble tumor necrosis factor receptor II (hsTNFR) linked to the Fc portion of human IgG1, is used to treat RA based on the rationale that sTNFR binds TNFα and blocks TNFα-mediated inflammation. We compared hsTNFR protein delivery from genetically engineered human mesenchymal stem cells (hMSCs) with etanercept. Blocking TNFα-dependent intercellular adhesion molecule-1 expression on transduced hMSCs and inhibition of nitric oxide production from TNFα-treated bovine chondrocytes by conditioned culture media from transduced hMSCs demonstrated the functionality of the hsTNFR construction. Implanted hsTNFR-transduced mesenchymal stem cells (MSCs) reduced mouse serum circulating TNFα generated from either implanted TNFα-expressing cells or lipopolysaccharide induction more effectively than etanercept (TNFα, 100%; interleukin [IL]-1α, 90%; and IL-6, 60% within 6 hours), suggesting faster clearance of the soluble tumor necrosis factor receptor (sTNFR)-TNFα complex from the animals. In vivo efficacy of sTNFR-transduced MSCs was illustrated in two (immune-deficient and immune-competent) arthritic rodent models. In the antibody-induced arthritis BalbC/SCID mouse model, intramuscular injection of hsTNFR-transduced hMSCs reduced joint inflammation by 90% compared with untransduced hMSCs; in the collagen-induced arthritis Fischer rat model, both sTNFR-transduced rat MSCs and etanercept inhibited joint inflammation by 30%. In vitro chondrogenesis assays showed the ability of TNFα and IL1α, but not interferon γ, to inhibit hMSC differentiation to chondrocytes, illustrating an additional negative role for inflammatory cytokines in joint repair. The data support the utility of hMSCs as therapeutic gene delivery vehicles and their potential to be used in alleviating inflammation within the arthritic joint.

Few US clinical laboratories screen stool specimens for Shiga toxin-producing Escherichia coli (STEC) other than E. coli O157. An outbreak of STEC O111:H8 infections indistinguishable from E. coli O157:H7 at a youth camp highlights the need to improve non-O157 STEC surveillance. Interviews of 521 (80%) of 650 attendees revealed 55 (11%) were ill; 2 developed hemolytic-uremic syndrome. Illness was associated with consuming salad during the camp's first lunch meal (hazard ratio [HR], 4.68; P<.01), consuming ice provided in barrels on the camp's final day (HR, 3.41; P<.01), eating cob corn (HR, 3.22; P<.01), and eating a dinner roll (HR, 2.82; P<.01). Cultures of 2 of 11 stools yielded E. coli O111:H8. Results of serologic testing and additional stool cultures demonstrated no evidence of infection with other bacterial pathogens, including E. coli O157, and supported infection with E. coli O111. Clinical laboratories should routinely screen suspect specimens for non-O157 STEC and should serotype and report Shiga-positive isolates.

Foodborne botulism is caused by potent neurotoxins of Clostridium botulinum. We investigated a large outbreak of foodborne botulism among church supper attendees in Texas. We conducted a cohort study of attendees and investigated the salvage store that sold the implicated foods. We identified 15 cases of botulism (40%) among 38 church supper attendees. Nine patients (60%) had botulinum toxin type A detected in stool specimens. The diagnosis was delayed in 3 cases. Fifteen (63%) of 24 attendees who ate a chili dish developed botulism (relative risk, undefined; P<.001). The chili dish was prepared with "brand X" or "brand Y" frozen chili, "brand Z" canned chili, and hot dogs. An unopened container of brand X chili yielded type A toxin. Brand X chili was purchased at a salvage store where perishable foods were inadequately refrigerated. Our investigation highlights the need to improve clinicians' awareness of botulism. More rigorous and more unannounced inspections may be necessary to detect food mishandling at salvage stores.

Benzalkonium chloride (BC) continues to be used as an antiseptic and contributes to serious outbreaks of disease. In July 1999, 6 postinjection joint infections caused by Mycobacterium abscessus were reported to the Texas Department of Health (Austin). We investigated this outbreak and identified 12 case patients who had been seen by the same physician and who had received an intra-articular or periarticular steroid injection during the period of 1 April through 31 July 1999. M. abscessus was cultured from either joint fluid or periarticular soft-tissue specimens obtained from 10 patients. We cultured environmental samples, and we compared isolates recovered from case patients with environmental isolates by pulsed-field gel electrophoresis and randomly amplified polymorphic DNA polymerase chain reaction (RAPD-PCR). Four environmental samples containing diluted BC yielded M. abscessus. Clinical and environmental strains of M. abscessus were indistinguishable by RAPD-PCR. The case patients' strain was resistant to BC. The use of BC as an antiseptic should be discontinued.

The dietary intake of micronutrients and serum micronutrient status have been topics of concern in relation to human immunodeficiency virus (HIV) progression. Most data, however, were collected prior to the introduction of protease inhibitors (PIs). We analyzed dietary intake and serum values of vitamin B(12), including the effect of PIs, in a cohort of persons with HIV infection. During intervals with no PI use, each 1 microg/day increase in B(12) intake was associated with a 1.06 pg/mL increase in serum B(12) levels. However, during intervals with PI use, each 1 microg/day increase in intake was associated with only a 0.12 increase in serum B(12) levels. Adequate serum B(12) levels (>350 pg/mL) cannot be assumed even in the presence of PIs, and dietary supplementation may not be adequate to significantly increase serum B(12) levels. Serum B(12) levels should be determined yearly in persons with HIV infection, regardless of whether they are receiving PI treatment.

Populations of Mexican descent have high occurrences of neural tube defects (NTDs). A recent study suggested that folic acid supplements may not protect these populations from NTDs. In a case-control study, the authors investigated the role of folic acid and dietary folate intake in NTD risk among Mexican Americans living along the Texas-Mexico border. From January 1995 to February 1999, 148 Mexican-American women with NTD-affected pregnancies and 158 women with normal live births were interviewed in person about use of vitamin supplements and dietary intakes during a 6-month periconceptional period (from 3 months before conception to 3 months after conception). Daily preconceptional consumption of vitamin supplements containing folic acid was 2.5% in control women and 2.0% in case women (odds ratio = 0.77; 95% confidence interval (CI): 0.19, 3.22). With adjustment for maternal age, education, obesity, and previous stillbirth or miscarriage, the risk estimate was essentially null (odds ratio = 1.12; 95% CI: 0.22, 5.78). Combined folic acid intake from diet and supplements showed only a modest risk reduction for intakes of > or = 1.0 mg per day (adjusted odds ratio = 0.73; 95% CI: 0.31, 1.72). The fact that the primary folic acid exposure was in the form of dietary polyglutamates rather than the more easily absorbed supplemental monoglutamates may explain an apparent decreased effect in this population.

In March 1998, an outbreak of acute gastroenteritis occurred among students at a Texas university. Overall, 125 ill students sought medical care. Case-control studies revealed that illness was significantly associated with eating foods from the university's main cafeteria deli bar on 9 and 10 March. Stool specimens from 9 (50%) of 18 ill students and samples of deli ham showed evidence of Norwalk-like viruses (NLVs) by reverse-transcriptase (RT) polymerase chain reaction (PCR) assay. A food handler who prepared sandwiches for lunch on 9 March reported that her infant had been sick with watery diarrhea since just before the outbreak. A stool sample from the infant was positive for NLV by RT-PCR, and the sequence of the amplified product was identical to that of amplified product from deli ham and students' stool specimens. This is the first time RT-PCR and sequence analysis have successfully confirmed viral contamination of a food item likely to have been contaminated by a food handler.

In response to a 1991 anencephaly cluster in Cameron County, Texas, a surveillance and neural tube defect (NTD) recurrence prevention project for NTDs was implemented in the 14 Texas-Mexico border counties. For 1993-1995, NTD-affected pregnancies were identified at all gestational ages through active surveillance of multiple case-ascertainment sources. There were 87 cases of anencephaly, 96 cases of spina bifida, and 14 cases of encephalocele for respective rates of 6.4, 7.1, and 1.1 per 10,000 live births. Of the 197 NTD case-women, 93% were Hispanic. The overall, Hispanic, and Anglo NTD rates were, respectively, 14.6, 14.9, and 10.6 per 10,000 live births. The NTD rate for El Paso County (9.8 per 10,000), the most northwestern Texas county, was significantly lower (p = 0.001) than the aggregate rate for the rest of the Texas border (17.1 per 10,000). The overall Texas border rate was significantly higher (p < 0.001) than a recently estimated rate of 9.3 for California and minimally higher than a recently adjusted rate of 11.3 for the Metropolitan Atlanta Congenital Defects Program counties (p = 0.052), both of which now reflect all gestational ages. Of the 197 Texas border cases, 85% (168 cases) reached a gestational age of > or =20 weeks. Excluding cases of <20 weeks' gestation in the rate had a more marked effect on reducing the anencephaly rate (4.9 per 10,000) than the spina bifida rate (6.7 per 10,000). A country of birth was known for 153 (83%) of the 184 Hispanic case-women: 63% were born in Mexico; 24%, in Texas; and 11%, elsewhere in the United States. Rates for Mexico-born Hispanic women (15.1 per 10,000) were significantly higher than rates for United States-born Hispanic women (9.5 per 10,000) (p = 0.006).

The influence of infection-control practices on bloodstream infection (BSI) risk was examined in a home health care setting in which three needleless devices were used consecutively. A case-control study and a retrospective cohort study were conducted. Risk factors for BSI included lower education level, younger age, having a central venous catheter (CVC) with multiple ports, or having a tunneled CVC. Among patients with a tunneled CVC, those at greatest risk had been allowed to shower rather than bathe and to get their exit site wet (P<.01). A high proportion (49%) of isolates were hydrophilic gram-negative bacteria, suggesting water sources of infection. In the cohort study, the BSI rate decreased as the frequency of changing the needleless device end cap increased from once weekly up to every 2 days, suggesting that the mechanism for BSI may involve contamination from the end cap. These findings may help to develop infection-control measures specific to home health care.

In April 1996, laboratory testing of imported nonhuman primates (as mandated by quarantine regulations) identified 2 cynomolgus macaques (Macaca fascicularis) infected with Ebola (subtype Reston) virus in a US-registered quarantine facility. The animals were part of a shipment of 100 nonhuman primates recently imported from the Philippines. Two additional infected animals, who were thought to be in the incubation phase, were identified among the remaining 48 animals in the affected quarantine room. The other 50 macaques, who had been held in a separate isolation room, remained asymptomatic, and none of these animals seroconverted during an extended quarantine period. Due to the rigorous routine safety precautions, the facility personnel had no unprotected exposures and remained asymptomatic, and no one seroconverted. The mandatory quarantine and laboratory testing requirements, put in place after the original Reston outbreak in 1989-1990, were effective for detecting and containing Ebola virus infection in newly imported nonhuman primates and minimizing potential human transmission.

In April 1994, the largest outbreak of botulism in the United States since 1978 occurred in El Paso, Texas. Thirty persons were affected; 4 required mechanical ventilation. All ate food from a Greek restaurant. The attack rate among persons who ate a potato-based dip was 86% (19/22) compared with 6% (11/176) among persons who did not eat the dip (relative risk [RR] = 13.8; 95% confidence interval [CI], 7.6-25.1). The attack rate among persons who ate an eggplant-based dip was 67% (6/9) compared with 13% (241189) among persons who did not (RR = 5.2; 95% CI, 2.9-9.5). Botulism toxin type A was detected from patients and in both dips. Toxin formation resulted from holding aluminum foil-wrapped baked potatoes at room temperature, apparently for several days, before they were used in the dips. Consumers should be informed of the potential hazards caused by holding foil-wrapped potatoes at ambient temperatures after cooking.

Morbidity and mortality data for young women in the United States reflect several health risk behaviors for both acute and chronic disease development. Available data suggest that young women's diets are high in total and saturated fat and low in fiber, fruits, vegetables, and dairy products. As a result, diets of young women are frequently low in iron, folate, and calcium. Prevalence of overweight continues to increase significantly in this population, but inappropriate body image concerns and disordered eating patterns are also common. Inactivity, smoking, and weight cycling are patterns that appear to begin early in women's lives. Some data suggest that young women value nutrition quality and are more likely to attempt positive changes than are young men.

From February through April 1989, four outbreaks of staphylococcal food poisoning in the United States were associated with eating mushrooms canned in the People's Republic of China (PRC). In the four outbreaks, 99 persons who ate at a suspect facility developed gastrointestinal symptoms within 24 h, including 18 who were hospitalized. Illness was associated with eating mushrooms at a university cafeteria (relative risk [RR] = 53.0), a hospital cafeteria (RR = 13.8), a pizzeria (odds ratio [OR] = infinity), and a restaurant (OR = infinity) (all P < .0001). Staphylococcal enterotoxin A was found by ELISA in mushrooms at the sites of two outbreaks and in unopened cans from the three plants thought to have produced mushrooms implicated in outbreaks. These investigations led to multistate recalls and a US Food and Drug Administration order to restrict entry into the United States of all mushrooms produced in the PRC; until this action, the United States imported approximately 50 million pounds yearly.

Current weaning recommendations are based on nutritional need, physiologic maturation, and the behavioral and developmental aspects of infant feeding. Inadequate energy and protein intake and deficiencies of iron, zinc, vitamin A, and vitamin D are the most commonly observed nutrient deficiencies during infancy and weaning recommendations have focused on their prevention. This article reviews the data and summarizes implications for infant weaning in both developed and developing countries. Current published recommendations for infant feeding are outlined and major concerns are highlighted.