Review of brucellosis cases from laboratory exposures in the United States in 2008 to 2011 and improved strategies for disease prevention.

Five laboratory-acquired brucellosis (LAB) cases that occurred in the United States between 2008 and 2011 are presented. The Centers for Disease Control and Prevention (CDC) reviewed the recommendations published in 2008 and the published literature to identify strategies to further prevent LAB. The improved prevention strategies are described.

Preparedness and health risks associated with Moulay Abdellah Amghar moussem, Morocco, 2009-2010.

The objective of this study was to describe the risks and human health outcomes associated with attendance at the Moulay Abdellah Amghar moussem (a pre-planned mass gathering attracting more than 360 000 participants) for the purposes of public health prevention, planning, preparedness and response. We performed an environmental health risk assessment and retrospectively reviewed local health centre records before, during and after the event. In addition, standardized interviews with key stakeholders were performed to qualitatively evaluate local public health preparedness and response capacities. During the event, average daily health centre visits increased 5-fold. The sex ratio of health-care visits changed significantly from an average of 1.8:1 female:male visits per day to 1.2:1. The proportion of injuries varied from an average of 3.7% pre- and post-event to 14.8% (P < 0.01) during the event. A significant increase in digestive diseases was also observed during the event. Recommendations include increasing accessibility to free sanitation and hygiene facilities and improving health communications concerning hand washing and food and water safety.

Public health considerations for mass gatherings in the Middle East and North Africa (MENA) region.

This review describes major mass gatherings in the MENA region and the public health implications of these events, and provides recommendations for public health officials of the host country. Through our search of the literature for peer-reviewed publications, we identified relevant 77 papers; all were related to the annual Hajj. Using the information obtained from the literature review, the Eastern Mediterranean Public Health Network (EMPHNET) and the Centers for Disease Control and Prevention (CDC) developed and conducted 2 workshops on Public Health Surveillance during Mass Gatherings for field epidemiology training programmes and ministry of health focal points from 10 countries. The main potential public health concerns associated with mass gatherings include: infectious diseases (e.g. respiratory disease, gastro-intestinal tract disease, foodborne disease), injuries, traffic accidents, heat-related illnesses, insect stings, non-communicable diseases and terrorism.

Fatal Apophysomyces elegans infection transmitted by deceased donor renal allografts.

Two patients developed renal mucormycosis following transplantation of kidneys from the same donor, a near-drowning victim in a motor vehicle crash. Genotypically, indistinguishable strains of Apophysomyces elegans were recovered from both recipients. We investigated the source of the infection including review of medical records, environmental sampling at possible locations of contamination and query for additional cases at other centers. Histopathology of the explanted kidneys revealed extensive vascular invasion by aseptate, fungal hyphae with relative sparing of the renal capsules suggesting a vascular route of contamination. Disseminated infection in the donor could not be definitively established. A. elegans was not recovered from the same lots of reagents used for organ recovery or environmental samples and no other organ transplant-related cases were identified. This investigation suggests either isolated contamination of the organs during recovery or undiagnosed disseminated donor infection following a near-drowning event. Although no changes to current organ recovery or transplant procedures are recommended, public health officials and transplant physicians should consider the possibility of mucormycosis transmitted via organs in the future, particularly for near-drowning events. Attention to aseptic technique during organ recovery and processing is re-emphasized.

Implementation of laboratory order data in BioSense Early Event Detection and Situation Awareness System.

INTRODUCTION: Laboratory test orders constitute an early outbreak data source. CDC receives laboratory order data in HL7 format from the Laboratory Corporation of America (LabCorp) and plans to use the data in the BioSense Early Event Detection and Situation Awareness System. METHODS: These LabCorp data contain information on tests ordered and include the type of test ordered and the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM)-coded reasons for the order. A consensus panel was formed to group test orders on the basis of expert opinion into eight standard syndrome categories to provide an additional data source for early outbreak detection. A laboratory order taxonomy was developed and used in the mapping consolidation phase. The five main classes of this taxonomy are miscellaneous functional tests, fluid screening tests, system-specific tests, tests for specific infections (by primary manifestation), and tests for specific noninfectious diseases. RESULTS: Summary of numbers of laboratory order codes in each syndrome category are fever (53), respiratory (53), gastrointestinal (27), neurological (35), rash (37), lymphadenitis (20), localized cutaneous lesion (11), and specific infection (63). CONCLUSION: With the daily use of laboratory order data in BioSense, the actual distribution of laboratory order codes in syndrome groups can be evaluated, allowing modification of the mapping.

Risk of duodenal adenoma in celiac disease.

BACKGROUND: There is a 60- to 80-fold increased risk of small-bowel adenocarcinoma in patients with celiac disease. While the adenoma-carcinoma sequence appears to operate in the small bowel as in the large bowel, the risk of duodenal adenomas in celiac patients is unknown. METHODS: The records of 381 patients (245 F, 136 M) with biopsy-proven celiac disease were reviewed to determine the prevalence of duodenal adenoma found during esophagogastroduodenoscopy (EGD). We conducted an extensive literature review to find data for estimates of the prevalence of duodenal adenoma in a comparable general population; we used data from a study at another New York City medical center of 7346 EGDs conducted between 1976 and 1982 (Ghazi et al., 1984). We estimated the relative risk, expressed as a standard morbidity ratio (SMR), by calculating the observed to expected (O/E) ratio. RESULTS: Duodenal adenomas were found in 3 celiac patients (0.78%), with 24 adenomas (0.33%) in the reference population, giving an SMR of 2.39 (95% CI 0.67-8.48). CONCLUSION: We did not find a significantly increased risk of duodenal adenoma in celiac patients compared to a non-celiac endoscoped population. Thus, despite the previously described elevated risk of small-bowel adenocarcinoma in these patients, routine endoscopic examination of the duodenum may not be adequate for screening.

Garlic and cancer: a critical review of the epidemiologic literature.

Animal and in vitro studies provide evidence of an anticarcinogenic effect of active ingredients in garlic. This review of the epidemiologic literature on garlic consumption addresses cancers of the stomach, colon, head and neck, lung, breast and prostate. Nineteen studies reported relative risk estimates for garlic consumption and cancer incidence. Site-specific case-control studies of stomach and colorectal cancer, in which multiple reports were available, suggest a protective effect of high intake of raw and/or cooked garlic. Cohort studies confirm this inverse association for colorectal cancer. Few cohort and case-control studies for other sites of cancer exist. Garlic supplements, as analyzed in four cohort studies and one case-control report, from two distinct populations, do not appear to be related to risk. Low study power, lack of variability in garlic consumption categorization within studies and poor adjustment for potential cofounders may limit the reliability of any conclusions regarding garlic supplements. However, an indication of publication bias was also found by visual inspection of a funnel plot and in a log-rank test (P = 0.004). Evidence from available studies nevertheless suggests a preventive effect of garlic consumption in stomach and colorectal cancers. The study limitations indicate the need for more definitive research and improved nutritional epidemiologic analyses of dietary data.

Dietary antioxidants, supplements, and risk of epithelial ovarian cancer.

Several studies of dietary and serum antioxidant micronutrients (vitamins A, C, and E and beta-carotene) suggest that higher levels may be protective for ovarian cancer. None of these has examined supplements. We used a food frequency questionnaire and additional questions on supplements to study 168 histologically confirmed epithelial ovarian cancer cases, 159 community controls, and 92 hospital-based controls. Antioxidant consumption from diet or supplements was calculated in milligrams or international units per day. In multivariate analyses using only community controls, the highest levels of intake of vitamins C and E from supplements were protective: odds ratio (OR) = 0.40 [95% confidence interval (CI) = 0.21-0.78] and OR = 0.33 (95% CI = 0.18-0.60), respectively. Consumption of antioxidants from diet was unrelated to risk. In analyses combining antioxidant intake from diet and supplements, vitamins C (> 363 mg/day) and E (> 75 mg/day) were associated with reduced risks: OR = 0.45 (95% CI = 0.22-0.91) and OR = 0.44 (95% CI = 0.21-0.94), respectively. Results were similar, with some attenuation toward the null, in analyses combining both control groups. The levels of vitamins C and E associated with the protective effect were well above the current US Recommended Dietary Allowances. These findings support the hypothesis that antioxidant vitamins C and E from supplements are related to a reduced risk of ovarian cancer.

Garlic consumption and cancer prevention: meta-analyses of colorectal and stomach cancers.

BACKGROUND: Animal and in vitro studies have provided evidence of an anticarcinogenic effect of active ingredients in garlic. OBJECTIVE: The objective was to conduct meta-analyses of the epidemiologic literature on the association between garlic consumption and risk of stomach, colon, head and neck, lung, breast, and prostate cancers. DESIGN: Meta-analyses were conducted for all cancers mutually and separately for colorectal and stomach cancers in relation to consumption of exclusively raw garlic, cooked garlic, or both (RC garlic). Eighteen studies reported a relative risk estimate for RC garlic consumption and cancer risk. RESULTS: In the meta-analyses of colorectal and stomach cancer, the reference categories ranged from no consumption to consumption of 3.5 g/wk, whereas the highest categories ranged from any consumption to >28.8 g/wk. The average difference between the highest and lowest categories was 16 g/wk. The random-effects relative risk (RR) estimate of colorectal cancer and RC garlic consumption, excluding garlic supplements, was 0.69 (95% CI: 0.55, 0.89). For stomach cancer, the random-effects RR estimate was 0.53 (95% CI: 0.31, 0.92). The heterogeneity among studies for the latter outcome (P: = 0.0002) indicates the questionableness of the generalizability of this summary estimate. An indication of publication bias for all cancers combined is evident from a funnel plot of RC garlic consumption and cancer risk and from the results of the Begg and Mazumdar test (P: = 0.049). CONCLUSIONS: High intake of RC garlic may be associated with a protective effect against stomach and colorectal cancers. Heterogeneity of effect estimates, differences in dose estimation, publication bias, and possible alternative hypotheses (eg, confounding by total vegetable consumption) preclude sole reliance on summary effect estimates.

Clinical study of 9-cis retinoic acid (LGD1057) in acute promyelocytic leukemia.

The use of all-trans retinoic acid (RA) for remission induction markedly increases survival of patients with acute promyelocytic leukemia (APL) compared to patients treated solely with cytotoxic chemotherapy. However, clinical resistance to this agent develops rapidly, which has been associated with a progressive decline in plasma drug concentrations. Previous studies suggested that 9-cis RA, a retinoid receptor 'pan agonist' did not induce its own catabolism to the same extent as all-trans RA. Therefore, we conducted a dose-ranging study of this compound in patients with both relapsed and newly diagnosed APL. We treated 18 patients with morphologically diagnosed APL (13 relapsed, five newly diagnosed). The daily dose of 9-cis RA ranged from 30 to 230 mg/m2/day given as a single oral dose. Four of 12 (33%) relapsed patients (three of whom were previously treated with all-trans RA) and four of five (80%) newly diagnosed patients achieved complete remission. The sole failure in the newly diagnosed group died early from an intracranial hemorrhage. One other patient with t(9;12) translocation had substantial hematologic improvement. The drug was generally well tolerated; headache and dry skin were the most common adverse reactions. Three patients were treated with corticosteroids for signs of incipient 'RA syndrome.' These preliminary data suggest that 9-cis RA is an effective agent for remission induction and deserves further investigation in patients with retinoid-sensitive APL.

Phase I study of tirapazamine and cisplatin in patients with recurrent cervical cancer.

OBJECTIVES: Tirapazamine (SR 4233) is a benzotriazine compound exhibiting substantial differential toxicity for hypoxic cells. A large enhancement in tumor cell killing has been demonstrated in preclinical studies when tirapazamine was combined with cisplatin. This phase I study was undertaken to establish a safe dose combination of tirapazamine and cisplatin when administered to patients with recurrent cervical carcinoma. METHODS: Tirapazamine was administered as an intravenous infusion over 2 hr, followed 1 hr later by cisplatin intravenously over 1 hr, every 21 days. All patients received prophylactic antiemetics consisting of ondansetron, dexamethasone, and lorazepam. The planned dose escalation levels of tirapazamine were 195, 260, 330, and 390 mg/m2. The cisplatin dose was fixed at 75 mg/m2. RESULTS: A total of 12 patients were treated with 43 courses of therapy. Patients were heavily pretreated. Eleven of the 12 had prior radiotherapy and 5 of the 12 had prior cisplatin-based chemotherapy. A maximally tolerated dose of 330 mg/m2 was defined for this patient population. The dose-limiting toxicity was nausea and vomiting. All 12 patients were also evaluated for response. Two major responses were seen (17%). In addition, there were three minor responses (25%) and 4 patients achieved disease stabilization (33%). All major and minor responses were seen at the highest dose level tested of 330 mg/m2. CONCLUSIONS: Tirapazamine and cisplatin is an interesting drug combination in the treatment of cervical cancer. Phase II testing is planned.

All-trans retinoic acid significantly increases 5-year survival in patients with acute promyelocytic leukemia: long-term follow-up of the New York study.

All-trans retinoic acid (ATRA) induces a high incidence of complete remission (CR) in patients with acute promyelocytic leukemia (APL); however, the magnitude of this agent's contribution to increased rates of cure of this disease has not yet been established. From 1990 to 1995 we used RA as remission induction therapy in 103 APL patients (73 newly diagnosed and 30 previously treated) who were retinoid-naive and were treated on the basis of initial morphology. Patients whose diagnosis was changed on the basis of the results of molecular testing (n = 13) were withdrawn from RA treatment and given chemotherapy alone. After achieving a CR, previously untreated patients received several cycles of consolidation chemotherapy, usually with idarubicin and cytosine arabinoside. Among individuals whose diagnosis was molecularly confirmed, 54 of 65 new patients (83%) and 25 of 30 previously treated patients (83%) achieved a CR. All induction failures in molecularly diagnosed cases were due either to early death or to premature withdrawal. Median disease-free and overall survival rates recorded for all newly diagnosed patients are currently > 40+ and > 43+ months, respectively. We subsequently examined a subset of 27 newly diagnosed patients treated during the first 2 years of this program whose actual median follow-up period is now > 5 years. Median disease-free and overall survival rates recorded for this group are > 57+ and > 58+ months, respectively; 56% of these patients are alive in first remission. These results significantly exceed those achieved using chemotherapy alone in a historical control group of 80 patients consecutively treated at this center from 1975 to 1990, whose median disease-free and overall survival rates were 11 and 19 months, respectively; only 22% of these patients were alive in first remission at 5 years. Although a high proportion of previously treated patients also achieved a CR after RA treatment, median disease-free and overall survival rates noted for that group were markedly lower (i.e., 7.5 and 10.9 months, respectively). Thus, data from patients whose median follow-up period is now > 5 years have confirmed earlier projections and indicate that the use of RA for remission induction yields an approximately 2.5-fold increase in the proportion of patients who have presumably been cured of this disease.