Obesity in neurology practice: a call to action
Trevathan E , Dietz WH . Neurology 2009 73 (9) 654-5 Childhood obesity, defined as a body mass index (BMI; weight [kg]/height [m2]) ≥95th percentile for children or adolescents of the same age and sex, now affects 16% of 2- to 19-year-olds in the United States. An additional 15% are overweight, defined as a BMI between the 85th and 95th percentiles.1 Recent estimates suggest that 70% of obese children have at least one additional cardiovascular disease risk factor, like elevated blood pressure, hyperlipidemia, or hyperinsulinemia, and almost 40% have 2 or more.2 The obesity epidemic among children is now a national crisis to which we must all respond. | In this issue of Neurology®, researchers from Cincinnati Children’s Hospital raise the possibility that obesity is associated with new onset childhood epilepsy.3 In the selection of their control populations, the authors have tried to demonstrate that the increased prevalence of obesity among children with new onset seizures is unique to these patients and not a consequence of a sampling bias. Their observation that African Americans and Hispanics, among whom the prevalence of obesity is increased, were underrepresented in the new onset seizure group compared to a local control helps allay this concern about sampling. |
Prevalence of epilepsy and seizures in the Navajo Nation 1998-2002
Parko K , Thurman DJ . Epilepsia 2009 50 (10) 2180-5 PURPOSE: To determine the prevalence of epilepsy and seizures in the Navajo. METHODS: We studied 226,496 Navajo residing in the Navajo Reservation who had at least one medical encounter between October 1, 1998 and September 30, 2002. We ascertained and confirmed cases in two phases. First, we identified patients with International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes signifying epilepsy or seizures using Indian Health Service (IHS) administrative data. Second, we reviewed medical charts of a geographic subpopulation of identified patients to confirm diagnoses and assess the positive predictive value of the ICD-9-CM codes in identifying patients with active epilepsy. RESULTS: Two percent of Navajo receiving IHS care were found to have an ICD-9-CM code consistent with epilepsy or seizures. Based on confirmed cases, the crude prevalence for the occurrence of any seizure (including febrile seizures and recurrent seizures that may have been provoked) in the geographic subpopulation was 13.5 per 1,000 and the crude prevalence of active epilepsy was 9.2 per 1,000. Prevalence was higher among males, children under 5 years of age, and older adults. DISCUSSION: The estimated prevalence of active epilepsy in the Navajo Nation is above the upper limit of the range of reported estimates from other comparable studies of U.S. communities. |
Static knee alignment measurements among Caucasians and African Americans: the Johnston County Osteoarthritis Project
Nelson AE , Braga L , Braga-Baiak A , Atashili J , Schwartz TA , Renner JB , Helmick CG , Jordan JM . J Rheumatol 2009 36 (9) 1987-90 OBJECTIVE: To determine if knee alignment measures differ between African Americans and Caucasians without radiographic knee osteoarthritis (rOA). METHODS: A single knee was randomly selected from 175 participants in the Johnston County Osteoarthritis Project without rOA in either knee. Anatomic axis, condylar, tibial plateau, and condylar plateau angles were measured by 1 radiologist; means were compared and adjusted for age and body mass index (BMI). RESULTS: There were no significant differences in knee alignment measurements between Caucasians and African Americans among men or women. CONCLUSION: Observed differences in knee rOA occurrence between African Americans and Caucasians are not explained by differences in static knee alignment. |
Underlying cause of death in incident unprovoked seizures in the urban community of Northern Manhattan, New York City
Benn EK , Hauser WA , Shih T , Leary L , Bagiella E , Dayan P , Green R , Andrews H , Thurman DJ , Hesdorffer DC . Epilepsia 2009 50 (10) 2296-300 We determined underlying cause-specific mortality for incident unprovoked seizures from Northern Manhattan, New York City. We calculated the case fatality, proportionate mortality, and the underlying cause-specific standardized mortality ratios (SMRs), with U.S. death rates as the standard. Thirty-two deaths were observed between 2003 and 2007 among 209 participants. Case fatality was significantly lower for idiopathic/cryptogenic seizures versus symptomatic seizures. About 31.3% of the deaths were attributed to malignant neoplasms, 25.0% to diseases of the heart, 15.6% to influenza and pneumonia, 3.1% to cerebrovascular diseases, and 25.0% to other causes. Significant SMRs were observed for all causes (SMR = 1.6), influenza and pneumonia (SMR = 7.1), and malignant neoplasms (SMR = 2.9). Younger cases (<65 years) had increased SMRs for all causes, malignant neoplasms, and other causes. Older cases (> or =65 years) had increased SMRs for influenza and pneumonia. Underlying cause of death paralleled the underlying cause of seizure in patients with symptomatic etiologies. |
Aging with cerebral palsy and other disabilities: personal reflections and recommendations
Jones GC . Dev Med Child Neurol 2009 51 12-5 This article describes the lived experience of one 64-year-old woman who is aging with cerebral palsy (CP) and other multiple disabilities. Reflections are offered on coping with secondary conditions and functional decline; fighting the effects of pain and fatigue; and managing well-meaning, but misdirected, medical advice. Recommendations based on the author's personal and professional experience with disabilities, including CP, are presented on the aging process and on preventive care for adults living with CP. |
Policy statement--recommendations for the prevention and treatment of influenza in children, 2009 -2010
Committee on Infectious Diseases , Bell B , Fischer MA . Pediatrics 2009 124 (4) 1216-26 The purpose of this statement is to update current recommendations for routine use of trivalent seasonal influenza vaccine and antiviral medications for the prevention and treatment of influenza in children. |
Standardized treatment of active tuberculosis in patients with previous treatment and/or with mono-resistance to isoniazid: a systematic review and meta-analysis
Menzies D , Benedetti A , Paydar A , Royce S , Pai M , Burman W , Vernon A , Lienhardt C . PLoS Med 2009 6 (9) e1000150 BACKGROUND: A standardized regimen recommended by the World Health Organization for retreatment of active tuberculosis (TB) is widely used, but treatment outcomes are suspected to be poor. We conducted a systematic review of published evidence of treatment of patients with a history of previous treatment or documented isoniazid mono-resistance. METHODS AND FINDINGS: PubMed, EMBASE, and the Cochrane Central database for clinical trials were searched for randomized trials in previously treated patients and/or those with with mono-resistance to isoniazid, published in English, French, or Spanish between 1965 and June 2008. The first two sources were also searched for cohort studies evaluating specifically the current retreatment regimen. In studies selected for inclusion, rifampin-containing regimens were used to treat patients with bacteriologically confirmed pulmonary TB, in whom bacteriologically confirmed failure and/or relapse had been reported. Pooled cumulative incidences and 95% CIs of treatment outcomes were computed with random effects meta-analyses and negative binomial regression. No randomized trials of the currently recommended retreatment regimen were identified. Only six cohort studies were identified, in which failure rates were 18%-44% in those with isoniazid resistance. In nine trials, using very different regimens in previously treated patients with mono-resistance to isoniazid, the combined failure and relapse rates ranged from 0% to over 75%. From pooled analysis of 33 trials in 1,907 patients with mono-resistance to isoniazid, lower failure, relapse, and acquired drug resistance rates were associated with longer duration of rifampin, use of streptomycin, daily therapy initially, and treatment with a greater number of effective drugs. CONCLUSIONS: There are few published studies to support use of the current standardized retreatment regimen. Randomized trials of treatment of persons with isoniazid mono-resistance and/or a history of previous TB treatment are urgently needed. |
Effect of duration and intermittency of rifampin on tuberculosis treatment outcomes: a systematic review and meta-analysis
Menzies D , Benedetti A , Paydar A , Martin I , Royce S , Pai M , Vernon A , Lienhardt C , Burman W . PLoS Med 2009 6 (9) e1000146 BACKGROUND: Treatment regimens for active tuberculosis (TB) that are intermittent, or use rifampin during only the initial phase, offer practical advantages, but their efficacy has been questioned. We conducted a systematic review of treatment regimens for active TB, to assess the effect of duration and intermittency of rifampin use on TB treatment outcomes. METHODS AND FINDINGS: PubMed, Embase, and the Cochrane CENTRAL database for clinical trials were searched for randomized controlled trials, published in English, French, or Spanish, between 1965 and June 2008. Selected studies utilized standardized treatment with rifampin-containing regimens. Studies reported bacteriologically confirmed failure and/or relapse in previously untreated patients with bacteriologically confirmed pulmonary TB. Pooled cumulative incidences of treatment outcomes and association with risk factors were computed with stratified random effects meta-analyses. Meta-regression was performed using a negative binomial regression model. A total of 57 trials with 312 arms and 21,472 participants were included in the analysis. Regimens utilizing rifampin only for the first 1-2 mo had significantly higher rates of failure, relapse, and acquired drug resistance, as compared to regimens that used rifampin for 6 mo. This was particularly evident when there was initial drug resistance to isoniazid, streptomycin, or both. On the other hand, there was little evidence of difference in failure or relapse with daily or intermittent schedules of treatment administration, although there was insufficient published evidence of the efficacy of twice-weekly rifampin administration throughout therapy. CONCLUSIONS: TB treatment outcomes were significantly worse with shorter duration of rifampin, or with initial drug resistance to isoniazid and/or streptomycin. Treatment outcomes were similar with all intermittent schedules evaluated, but there is insufficient evidence to support administration of treatment twice weekly throughout therapy. |
Establishment of the 1st World Health Organization international standards for human papillomavirus type 16 DNA and type 18 DNA
Wilkinson DE , Baylis SA , Padley D , Heath AB , Ferguson M , Pagliusi SR , Quint WG , Wheeler CM , Collaborative Study Group , Unger E , Swan DC . Int J Cancer 2009 126 (12) 2969-83 A World Health Organization collaborative study was conducted to evaluate candidate International Standards for Human Papillomavirus (HPV) Type 16 DNA (NIBSC code 06/202) and HPV Type 18 DNA (NIBSC code 06/206) for use in the amplification and detection steps of nucleic acid-based assays. The freeze-dried candidate International Standards were prepared from bulk preparations of cloned plasmid containing full-length HPV-16 or HPV-18 genomic DNA. Nineteen laboratories from 13 countries participated in the study using a variety of commercial and in-house quantitative and qualitative assays. The data presented here indicate that, upon freeze-drying, there is no significant loss in potency for the candidate HPV-18 DNA and a slight loss in potency for the candidate HPV-16 DNA; although this is likely not scientifically relevant when assay precision is considered. In general, the individual laboratory mean estimates for each study sample were grouped +/- approximately 2 log(10) around the theoretical HPV DNA concentration of the reconstituted ampoule (1 x 10(7) HPV genome equivalents/mL). The agreement between laboratories is improved when potencies are made relative to the candidate International Standards, demonstrating their utility in harmonizing amplification and detection steps of HPV-16 and -18 DNA assays. Degradation studies indicate that the candidate International Standards are extremely stable and suitable for long-term use. Based on these findings, the candidate standards were established as the 1(st) WHO International Standards for HPV-16 DNA and HPV-18 DNA, each with a potency of 5 x 10(6) International Units (IU) per ampoule or 1 x 10(7) IU/mL when reconstituted as directed. (c) 2009 UICC. |
Evaluation of the survivability of MS2 viral aerosols deposited on filtering face piece respirator samples incorporating antimicrobial technologies
Rengasamy S , Fisher E , Shaffer RE . Am J Infect Control 2009 38 (1) 9-17 BACKGROUND: Respiratory protective devices exposed to pathogenic microorganisms present a potential source of transmission of infection during handling. In this study, the efficacy of 4 antimicrobial respirators to decontaminate MS2, a surrogate for pathogenic viruses, was evaluated and compared with control N95 filtering face piece respirators, which did not contain any known antimicrobial components. METHODS: MS2 containing droplet nuclei were generated using a Collison nebulizer and loaded onto respirator coupons at a face velocity of 13.2cm/seconds for 30minutes. The coupons were incubated at 2 different temperature and relative humidity (RH) conditions and analyzed for viable MS2 at different time intervals. RESULTS: Results showed that log(10) reduction of MS2 was not statistically significant (P > .05) between the control and antimicrobial respirator coupons, when stored at 22 degrees C and 30% RH up to 20hours. Coupons from 1 of the 4 antimicrobial respirators showed an average MS2log(10) reduction of 3.7 at 37 degrees C and 80% RH for 4hours, which was statistically significant (P ≤ .05) compared with coupons from the control respirators. CONCLUSION: Results from this study suggest that MS2 virus decontamination efficacy of antimicrobial respirators is dependent on the antimicrobial agent and storage conditions. |
Hospital-based surveillance of rotavirus diarrhea in the People's Republic of China, August 2003-July 2007
Duan ZJ , Liu N , Yang SH , Zhang J , Sun LW , Tang JY , Jin Y , Du ZQ , Xu J , Wu QB , Tong ZL , Gong ST , Qian Y , Ma JM , Liao XC , Widdowson MA , Jiang B , Fang ZY . J Infect Dis 2009 200 S167-73 Rotaviruses cause acute diarrhea worldwide. Previous studies of rotavirus diarrhea in China found that rotavirus infection is the most common cause of severe diarrhea in young children. In the present study, surveillance of rotavirus diarrhea was conducted involving 9549 children aged <5 years who were admitted for treatment of diarrhea at 11 sentinel hospitals in China from August 2003 through July 2007. Group A rotavirus was detected in 3749 (47.8%) of the 7846 fecal specimens by using enzyme-linked immunosorbent assay. Rotavirus isolates were characterized by reverse-transcriptase polymerase chain reaction to determine G and P genotypes. All the strains that are common worldwide were detected; G3P[8] was the most common. An unusual G5 strain was detected in 2 specimens. Of all episodes of rotavirus diarrhea, 94% occurred during the first 2 years of life, peaking at 6-23 months of age. Our findings indicate that globally common rotavirus strains continue to be a major cause of severe childhood diarrhea in China. Introduction of routine immunization with effective rotavirus vaccines would substantially reduce this burden. |
Infectious disease hospitalizations in the United States
Christensen KL , Holman RC , Steiner CA , Sejvar JJ , Stoll BJ , Schonberger LB . Clin Infect Dis 2009 49 (7) 1025-35 BACKGROUND: Infectious diseases (IDs) cause widespread morbidity and mortality. We describe the epidemiology of ID hospitalizations in the United States with use of a nationally representative database. METHODS: First-listed ID hospitalizations in the United States were analyzed using the Nationwide Inpatient Sample for 1998-2006. Hospitalization rates were calculated overall for IDs and for specific ID groups. RESULTS: An estimated 40,085,978 (standard error, 255,418) hospitalizations with a first-listed ID occurred during 1998-2006, for an age-adjusted hospitalization rate of 154.4 (95% confidence interval, 153.3-155.5) hospitalizations per 10,000 persons. The rate increased slightly over the study period (152.5 [95% confidence interval, 149.6-155.4] in 1998 vs 162.2 [95% confidence interval, 158.7-165.5] in 2006); an increase was seen for both sexes, for older patients, and for Hispanic patients. Among those aged 5-39 years, female patients had a significantly higher hospitalization rate than did male patients; male patients had higher rates among the youngest children and adults aged > or = 40 years. Approximately 4.5 million hospital days and $865 billion in hospital charges were associated with primary ID hospitalizations over the study period. Lower respiratory tract infections were the most commonly listed ID (34.4%), followed by kidney, urinary tract, and bladder infections; cellulitis; and abdominal and rectal infections. CONCLUSIONS: The ID hospitalization rate increased during 1998-2006, reflecting an increase in ID hospitalizations among adults aged > or = 30 years, particularly older adults. Differences in trends and patterns of ID hospitalizations were noted by sex, age group, and race. Lower respiratory tract infections accounted for the largest proportion of ID hospitalizations. Future efforts should focus on preventive measures and improving early interventions for IDs. |
Investigation of two outbreaks of suspected oral transmission of acute Chagas disease in the Amazon region, Para State, Brazil, in 2007
Beltrao Hde B , Cerroni Mde P , Freitas DR , Pinto AY , Valente Vda C , Valente SA , Costa Ede G , Sobel J . Trop Doct 2009 39 (4) 231-2 Acute Chagas disease (ACD) is caused by Trypanosoma cruzi. ACD outbreaks due to probable oral transmission occur regularly in small family gatherings that are exposed to contaminated foods. We studied two cohorts of residents on islands in the Breves and Bagre municipalities, in July and August 2007, to identify risk factors of transmission and to recommend preventative measures. Of the 25 cases identified in both cohorts, 13 (52%) were men, and the most frequent symptoms were fever (96%),asthenia (80%), myalgia (76%), abdominal pain (64%), retro-orbital pain, headaches and asthma (52%). We recommend detailed investigation of future outbreaks and other studies to better understand and control oral transmission of T. cruzi. |
Policy statement--guidance for the administration of medication in school
Council on School Health , Vernon-Smiley M . Pediatrics 2009 124 (4) 1244-51 Many children who take medications require them during the school day. This policy statement is designed to guide prescribing health care professionals, school physicians, and school health councils on the administration of medications to children at school. All districts and schools need to have policies and plans in place for safe, effective, and efficient administration of medications at school. Having full-time licensed registered nurses administering all routine and emergency medications in schools is the best situation. When a licensed registered nurse is not available, a licensed practical nurse may administer medications. When a nurse cannot administer medication in school, the American Academy of Pediatrics supports appropriate delegation of nursing services in the school setting. Delegation is a tool that may be used by the licensed registered school nurse to allow unlicensed assistive personnel to provide standardized, routine health services under the supervision of the nurse and on the basis of physician guidance and school nursing assessment of the unique needs of the individual child and the suitability of delegation of specific nursing tasks. Any delegation of nursing duties must be consistent with the requirements of state nurse practice acts, state regulations, and guidelines provided by professional nursing organizations. Long-term, emergency, and short-term medications; over-the-counter medications; alternative medications; and experimental drugs that are administered as part of a clinical trial are discussed in this statement. This statement has been endorsed by the American School Health Association. |
Lead and cognitive function in ALAD genotypes in the third National Health and Nutrition Examination Survey.
Krieg EF Jr , Butler MA , Chang MH , Liu T , Yesupriya A , Lindegren ML , Dowling N , CDC NCI NHANES III Genomics Working Group . Neurotoxicol Teratol 2009 31 (6) 364-71 The relationship between the blood lead concentration and cognitive function in children and adults with different ALAD genotypes who participated in the third National Health and Nutrition Examination Survey was investigated. The relationship between blood lead and serum homocysteine concentrations was also investigated. In children 12 to 16 years old, no difference in the relationship between cognitive function and blood lead concentration between genotypes was found. In adults 20 to 59 years old, mean reaction time decreased as the blood lead concentration increased in the ALAD rs1800435 CC/CG group. This represents an improvement in performance. In adults 60 years and older, no difference in the relationship between cognitive function and blood lead concentration between genotypes was found. The serum homocysteine concentration increased as the blood lead concentration increased in adults 20 to 59 years old and 60 years and older, but there were no differences between genotypes. The mean blood lead concentration of children with the ALAD rs1800435 CC/CG genotype was less than that of children with the GG genotype. |
Comparison of free radical generation by pre- and post-sintered cemented carbide particles
Stefaniak AB , Harvey CJ , Bukowski VC , Leonard SS . J Occup Environ Hyg 2010 7 (1) 23-34 Rapid generation of reactive oxygen species (ROS) may occur in response to cellular contact with metal particles. Generation of ROS by cobalt and/or tungsten carbide is implicated in causing hard metal lung disease (HMD) and allergic contact dermatitis (ACD). In this study, ROS generation and particle properties that influence radical generation were assessed for three sizes of tungsten, tungsten carbide, cobalt, admixture (tungsten carbide and cobalt powders), spray dryer, and post-sintered chamfer grinder powders using chemical (H(2)O(2) plus phosphate buffered saline, artificial lung surfactant, or artificial sweat) and cellular (RAW 264.7 mouse peritoneal monocytes plus artificial lung surfactant) reaction systems. For a given material, on a mass basis, hydroxyl (.OH) generation generally increased as particle size decreased; however, on a surface area basis, radical generation levels were more, but not completely, similar. Chamfer grinder powder, polycrystalline aggregates of tungsten carbide in a metallic cobalt matrix, generated the highest levels of .OH radicals (p < 0.05). Radical generation was not dependent on the masses of metals, rather, it involved surface-chemistry-mediated reactions that were limited to a biologically active fraction of the total available surface area of each material. Improved understanding of particle surface chemistry elucidated the importance of biologically active surface area in generation of ROS by particle mixtures. |
Lead poisoning among internally displaced Roma, Ashkali and Egyptian children in the United Nations-administered province of Kosovo
Brown MJ , McWeeney G , Kim R , Tahirukaj A , Bulat P , Syla S , Savic Z , Amitai Y , Dignam T , Kaluski DN . Eur J Public Health 2009 20 (3) 288-92 BACKGROUND: This study assessed the association between lead poisoning prevention activities and blood lead levels (BLLs) among children living in lead-contaminated camps for internally displaced persons in the United Nations-Administered Province of Kosovo. METHODS: We conducted a population-based study to examine the relationship among geometric mean BLLs in children (i) born before any lead poisoning prevention activities were instituted, (ii) born when specific interim interventions were instituted and (iii) born after relocation and medical therapy were available. The study population consisted of 145 of the 186 children born in the camps between December 1999 and July 2007. RESULTS: Lower mean BLLs were found in children born following implementation of the interventions as compared with the children born before the interventions. However, this decrease in mean BLLs was attenuated in children born into families suspected of informal lead smelting. CONCLUSION: Despite lower BLLs following interventions, children living in these camps have BLLs that remain unacceptably high. Further efforts are urgently needed to control or eliminate lead exposure in this population. Continued blood lead monitoring of the population is also warranted. |
Pesticide concentrations in maternal and umbilical cord sera and their relation to birth outcomes in a population of pregnant women and newborns in New Jersey
Barr DB , Ananth CV , Yan X , Lashley S , Smulian JC , Ledoux TA , Hore P , Robson MG . Sci Total Environ 2009 408 (4) 790-5 We evaluated in utero exposures to pesticides by measuring maternal and cord serum biomarkers in a New Jersey cohort of pregnant women and the birth outcomes of their neonates. The study was based on 150 women that underwent an elective cesarean delivery at term in a hospital in central New Jersey. We evaluated the following pesticide compounds in both maternal and umbilical cord sera: chlorpyrifos, diazinon, carbofuran, chlorothalonil, dacthal, metolachlor, trifluralin and diethyl-m-toluamide (DEET). Of these compounds, chlorpyrifos, carbofuran, chlorothalonil, trifluralin, metolachlor and DEET were the pesticides most frequently detected in the serum samples. We found high (≥75th percentile) metolachlor concentrations in cord blood that were related to birth weight (3605g in upper quartile vs 3399g; p=0.05). We also observed an increase in abdominal circumference with increasing cord dichloran concentrations (p=0.031). These observations suggest that in utero exposures to certain pesticides may alter birth outcomes. |
Urinary paranitrophenol, a metabolite of methyl parathion, in Thai farmer and child populations
Panuwet P , Prapamontol T , Chantara S , Thavornyuthikarn P , Bravo R , Restrepo P , Walker RD , Williams BL , Needham LL , Barr DB . Arch Environ Contam Toxicol 2009 57 (3) 623-9 Human exposure to methyl parathion can be assessed by measuring the concentration of its metabolite paranitrophenol (PNP) in urine. Our biologic monitoring study in Chiang Mai, Thailand, measured PNP and dialkylphosphate metabolites (i.e., dimethylphosphate [DMP] and dimethylthiophosphate [DMTP]) of methyl parathion in urine samples collected from 136 farmers (age 20 to 65 years) and 306 school children (age 10 to 15 years) in 2006. Participants came from two topographically different areas: one was colder and mountainous, whereas the other was alluvial with climate fluctuations depending on the monsoon season. Both children and farmers were recruited from each area. Despite methyl parathion's prohibited use in agriculture in 2004, we detected PNP in >90% of all samples analyzed. We applied a nonparametric correlation test (PNP vs. DMP and DMTP) to determine whether the PNP found in most of the samples tested resulted from exposures to methyl parathion. DMP (Spearman's rho = 0.601 [p = 0.001] for farmers and Spearman's rho = 0.263 [p <0.001] for children) and DMTP (Spearman's rho = 0.296 [p = 0.003] for farmers and Spearman's rho = 0.304 [p<0.001] for children) were positively correlated with PNP, suggesting a common source for the three analytes, presumably methyl parathion or related environmental degradates. Although we found a modest correlation between the metabolites, our findings suggest that despite the prohibition, at least a portion (approximately 25% to 60%) of the PNP detected among farmers and children in Thailand may be attributed to exposure from continued methyl parathion use. |
Sentinel hospital-based surveillance of rotavirus diarrhea in Iran
Eesteghamati A , Gouya M , Keshtkar A , Najafi L , Zali MR , Sanaei M , Yaghini F , El Mohamady H , Patel M , Klena JD , Teleb N . J Infect Dis 2009 200 S244-7 BACKGROUND: Rotavirus is the most common causes of severe, acute diarrhea during childhood and is an important cause of morbidity and mortality in developing countries. We established active hospital-based surveillance of childhood diarrhea to assess the scope of severe rotavirus disease in Iran. METHODS: From May 2006 through April 2007, prospective surveillance of rotavirus diarrhea among children aged <5 years was conducted in 5 sentinel hospitals in Iran. Stool samples were tested for rotavirus using a commercially available enzyme immunoassay, and rotavirus-positive samples were genotyped using reverse-transcriptase polymerase chain reaction. RESULTS: Of 2198 children admitted to the hospital for acute gastroenteritis, 1298 (59.1%) had stool samples test positive for rotavirus by enzyme immunoassay. Of the rotavirus episodes, 85% occurred during the first 2 years of life, with the peak prevalence of severe rotavirus disease occurring from September through January. Among the 110 rotavirus-positive samples that were genotyped, G4P[8] was the most commonly detected rotavirus genotype (30.9% of strains). Other commonly detected genotypes included P[8] with G nontypeable (21.8%), G4 with P nontypeable (13.6%), G1[P8] (10.9%), and G2[P4] (5.5%). CONCLUSIONS: Rotavirus is the most common cause of severe diarrhea in Iran, which indicates that safe and effective rotavirus vaccination in Iran is a public health priority. |
G and P types of circulating rotavirus strains in the United States during 1996-2005: nine years of prevaccine data
Gentsch JR , Hull JJ , Teel EN , Kerin TK , Freeman MM , Esona MD , Griffin DD , Bielfelt-Krall BP , Banyai K , Jiang B , Cortese MM , Glass RI , Parashar UD , Collaborating laboratories of the National Rotavirus Strain Surveillance System . J Infect Dis 2009 200 S99-S105 BACKGROUND: Rotavirus vaccine was recommended for routine use among US infants in 2006. To provide prevaccine data, we conducted strain surveillance for 9 consecutive seasons during 1996-2005. METHODS: Using reverse-transcriptase polymerase chain reaction genotyping and nucleotide sequencing, we determined P/G genotypes of >3100 rotavirus strains collected in up to 12 cities each year from different US regions. RESULTS: The most prevalent strain globally, P[8] G1, was the most prevalent each year in the United States (overall, 78.5% of strains; range, 60.0%-93.9%), and 9.2% of the samples were P[4] G2, 3.6% were P[8] G9, 1.7% were P[8] G3, and 0.8% were P[8] G4. Genotype P[6] G9, which emerged in 1995, was detected continuously for several seasons (from 1996-1997 to 2000-2001, 0.2%-5.4%) but was not identified in the subsequent 4 seasons. Single or a few detections of rare genotypes (eg, P[6] G12, P[9] G6, and P[9] G3) were observed during several rotavirus seasons at frequencies of 0.5%-1.7% and, overall, comprised 0.6% of all the samples from the entire surveillance period. Several globally common strains in addition to G1, especially G2 and G9, circulated at high prevalence (33%-62%) in some cities during certain years. CONCLUSIONS: Almost 85% of strains during 1996-2005 had either a G or P antigen that is present in both RotaTeq (Merck) and Rotarix (GlaxoSmithKline). Monitoring of strains after introduction of rotavirus vaccines is important. |
Invited commentary: genes, environment, and hybrid vigor.
Gwinn M , Guessous I , Khoury MJ . Am J Epidemiol 2009 170 (6) 703-7 In the 1950s, case-control studies of smoking and lung cancer established a paradigm for epidemiologic studies of risk factors for chronic diseases. Since then, thousands of case-control studies have examined possible associations of countless risk factors with numerous diseases, rarely finding associations as strong or consistent as that of smoking with lung cancer. Recently, researchers have applied advances in molecular genetics to conduct candidate gene and genome-wide association studies of lung cancer. Skeptics among both epidemiologists and geneticists have argued that genomic research adds little value when most cases of disease can be attributed to a preventable exposure; however, well-conducted studies of gene-environment interactions that draw on data from more than 50 years of research in toxicology, pathophysiology, and behavioral science offer important models for the development of more comprehensive approaches to understanding the etiology of chronic diseases. |
Whole genome single nucleotide polymorphism based phylogeny of Francisella tularensis and its application to the development of a strain typing assay
Pandya GA , Holmes MH , Petersen JM , Pradhan S , Karamycheva SA , Wolcott MJ , Molins C , Jones M , Schriefer ME , Fleischmann RD , Peterson SN . BMC Microbiol 2009 9 213 BACKGROUND: A low genetic diversity in Francisella tularensis has been documented. Current DNA based genotyping methods for typing F. tularensis offer a limited and varying degree of subspecies, clade and strain level discrimination power. Whole genome sequencing is the most accurate and reliable method to identify, type and determine phylogenetic relationships among strains of a species. However, lower cost typing schemes are necessary in order to enable typing of hundreds or even thousands of isolates. RESULTS: We have generated a high-resolution phylogenetic tree from 40 Francisella isolates, including 13 F. tularensis subspecies holarctica (type B) strains, 26 F. tularensis subsp. tularensis (type A) strains and a single F. novicida strain. The tree was generated from global multi-strain single nucleotide polymorphism (SNP) data collected using a set of six Affymetrix GeneChip resequencing arrays with the non-repetitive portion of LVS (type B) as the reference sequence complemented with unique sequences of SCHU S4 (type A). Global SNP based phylogenetic clustering was able to resolve all non-related strains. The phylogenetic tree was used to guide the selection of informative SNPs specific to major nodes in the tree for development of a genotyping assay for identification of F. tularensis subspecies and clades. We designed and validated an assay that uses these SNPs to accurately genotype 39 additional F. tularensis strains as type A (A1, A2, A1a or A1b) or type B (B1 or B2). CONCLUSION: Whole-genome SNP based clustering was shown to accurately identify SNPs for differentiation of F. tularensis subspecies and clades, emphasizing the potential power and utility of this methodology for selecting SNPs for typing of F. tularensis to the strain level. Additionally, whole genome sequence based SNP information gained from a representative population of strains may be used to perform evolutionary or phylogenetic comparisons of strains, or selection of unique strains for whole-genome sequencing projects. |
Genomic events underlying the changes in adamantane resistance among influenza A(H3N2) viruses during 2006-2008
Deyde V , Garten R , Sheu T , Smith C , Myrick A , Barnes J , Xu X , Shaw M , Klimov A , Gubareva L . Influenza Other Respir Viruses 2009 3 (6) 297-314 Please cite this paper as: Deyde et al. (2009). Genomic events underlying the changes in adamantane resistance among influenza A(H3N2) viruses during 2006-2008. Influenza and Other Respiratory Viruses 3(6), 297-314.Background Adamantanes resistance in H3N2 viruses has been increasing since 2000, and in 2005-2006 reached nearly 100% in most countries, with the circulation of the N-lineage. In 2006-2007, however, a significant decrease in resistance was observed in many regions. Objectives To explore potential links between adamantane resistance and the A(H3N2) viruses that circulated between 2006 and 2008. Methods A total of 1451 Influenza A (H3N2) viruses collected globally in 2001-2008 were screened for the presence of adamantane resistance markers. A subset of 100 viruses representing the broad genetic and geographic spectrum of these viruses was selected for complete genome sequencing and phylogenetic analyses. Results Full genome sequence analysis of 2006-2007 viruses revealed co-circulation of four distinct genotypes, designated A-D. Phylogenetic analyses demonstrated reassortment between viruses from the N-lineage and other viruses that had circulated in prior seasons, including those bearing an adamantane sensitive marker. Genotype D viruses became dominant in late 2006-2007 and continued to be the main H3N2 genotype in 2007-2008. Viruses of this genotype retained all N-lineage genome segments except PB2 and NP, which were acquired through reassortment. Conclusions The decrease in adamantane resistance at that time was due to transient co-circulation of genotypes that emerged through reassortment. Our findings emphasize the importance of complete genome sequencing in understanding the complex nature of the relationship between influenza virus evolution and antiviral resistance. The recent emergence of the pandemic multi-reassortant H1N1 virus underscores the importance of whole genome sequence monitoring for rapid detection of such unusual and novel strains. |
Incorporating genetics and genomics in risk assessment for inhaled manganese: from data to policy
Curran CP , Park RM , Ho SM , Haynes EN . Neurotoxicology 2009 30 (5) 754-60 Manganese is an essential nutrient, and a healthy human with good liver and kidney function can easily excrete excess dietary manganese. Inhaled manganese is a greater concern, because it bypasses the body's normal homeostatic mechanisms and can accumulate in the brain. Prolonged exposure to high manganese concentrations (>1mg/m(3)) in air leads to a Parkinsonian syndrome known as "manganism." Of greatest concern are recent studies which indicate that neurological and neurobehavioral deficits can occur when workers are exposed to much lower levels (<0.2mg/m(3)) of inhaled manganese in welding fumes. Consequently, researchers at NIOSH are conducting a risk assessment for inhaled manganese. Novel components of this risk assessment include an attempt to quantify the range of inter-individual differences using data generated by the Human Genome Project and experimental work to identify genetically based biomarkers of exposure, disease and susceptibility. The difficulties involved in moving from epidemiological and in vivo data to health-based quantitative risk assessment and ultimately enforceable government standards are discussed. |
Breast cancer as a global health concern
Coughlin SS , Ekwueme DU . Cancer Epidemiol 2009 33 (5) 315-8 Public health data indicate that the global burden of breast cancer in women, measured by incidence, mortality, and economic costs, is substantial and on the increase. Worldwide, it is estimated that more than one million women are diagnosed with breast cancer every year, and more than 410,000 will die from the disease. In low- and middle-income countries (LMCs), the infrastructure and resources for routine screening mammography are often unavailable. In such lower resource settings, breast cancers are commonly diagnosed at late stages, and women may receive inadequate treatment, pain relief, or palliative care. There have been an increasing number of global health initiatives to address breast cancer including efforts by Susan G. Komen for the Cure((c)), the Breast Health Global Initiative (BHGI), the U.S. Centers for Disease Control and Prevention (CDC), the American Cancer Society, the National Cancer Institute (NCI), and ongoing work by leading oncology societies in different parts of the world. To support such initiatives, and to provide a scientific evidence base for health policy and public health decision making, there is a need for further health services research and program evaluations. Cancer registries can be invaluable in ascertaining the magnitude of cancer disease burden and its distribution in these countries. Additional data are needed for various geographic areas to assess resources required, cost-effectiveness, and humane approaches for preventing or controlling breast cancer in low resource settings in developing countries. |
First infant botulism case due to Clostridium botulinum type E worldwide
Luquez C , Dykes JK , Yu PA , Raphael BH , Maslanka SE . J Clin Microbiol 2009 48 (1) 326-8 Clostridium botulinum type E has been associated with botulism in adults, but never in infants. Infant botulism type E cases have been associated with neurotoxigenic strains of C. butyricum. We report the first infant botulism case due to C. botulinum type E worldwide. |
Globally mobile populations and the spread of emerging pathogens
Arguin PM , Marano N , Freedman DO . Emerg Infect Dis 2009 15 (11) 1713-14 During the past decade, the global public health community has been challenged by the emergence and rapid worldwide spread of novel influenza strains, severe acute respiratory syndrome, chikungunya virus, drug-resistant tuberculosis, and other conditions and pathogens. Modern transportation and increased tourism, business travel, and immigration contributed to dissemination of these high-impact pathogens. The effectiveness of interventions such as airport screening, travel restrictions, and other community mitigation measures remains uncertain. However, human migration has occurred for centuries and will continue, despite the threats posed by microbes. |
Health status of visitors and temporary residents, United States
Yanni EA , Marano N , Stauffer WM , Barnett ED , Cano M , Cetron MS . Emerg Infect Dis 2009 15 (11) 1715-20 Human mobility has always been associated with the spread of infection, and mobility of nonimmigrant visitors and temporary residents to the United States is increasing, from approximately 12 million in 1987 to approximately 37 million in 2007. Lack of information about the health status of these populations upon arrival and their need for and use of medical services in the United States hinders development of public health policy, education, and provision of adequate clinical care. After these issues and needs are clarified, intervention programs should be developed to increase access and decrease the disparities of care experienced by these populations. |
Trends in HIV prevalence, estimated HIV incidence, and risk behavior among men who have sex with men in Bangkok, Thailand, 2003-2007
van Griensven F , Varangrat A , Wimonsate W , Tanpradech S , Kladsawad K , Chemnasiri T , Suksripanich O , Phanuphak P , Mock P , Kanggarnrua K , McNicholl J , Plipat T . J Acquir Immune Defic Syndr 2009 53 (2) 234-9 BACKGROUND: Men who have sex with men (MSM) continue to be at high risk for HIV infection. Here we evaluate trends in HIV prevalence, estimated HIV incidence, and risk behavior among MSM in Bangkok, Thailand. METHODS: Between 2003 and 2007, 3 biennial cross-sectional HIV prevalence assessments were conducted among MSM in Bangkok, Thailand, using venue-day-time sampling. Oral fluid was tested for HIV infection; demographic and behavioral data were self-collected using hand-held computers. Estimates of annual HIV incidence in young MSM were derived as follows: (number of HIV infections/sum of [current age-age at start of anal intercourse]) x 100). Logistic and Poisson regression was used to evaluate trends in HIV prevalence, estimated HIV incidence, and risk behavior. FINDINGS: The overall HIV prevalence increased from 17.3% in 2003 to 28.3% in 2005 to 30.8% in 2007 (P < 0.001 for trend). The estimated HIV incidence among young MSM increased from 4.1% in 2003 to 6.4% in 2005, to 7.7% in 2007 (P < 0.02 for trend). The increase in HIV prevalence from 2005 to 2007 was not statistically significant. The proportion of men reporting anal sex and casual or steady male sex partners in the past 3 months significantly decreased, whereas the proportion reporting drug use and drug use during sex significantly increased. No increase was observed in the proportion of men reporting consistent condom use. INTERPRETATION: Our data suggest that after a strong increase from 2003 to 2005, the HIV prevalence among MSM in Bangkok may have begun to stabilize. Given the continuing high levels of risk behavior and the estimated high HIV incidence in young MSM, additional HIV preventive interventions are necessary. |
Associations of health risk factors and chronic illnesses with life dissatisfaction among U.S. adults: the Behavioral Risk Factor Surveillance System, 2006
Li C , Ford ES , Zhao G , Mokdad AH . Prev Med 2009 49 253-9 OBJECTIVE: To estimate the prevalence of life dissatisfaction and assess its associations with health risk factors and chronic illnesses in adults. METHODS: Data from the Behavioral Risk Factor Surveillance System in 2006 (n=341,140) were analyzed. Odds ratios (ORs) and their 95% confidence intervals (CIs) were estimated using logistic regression analyses. RESULTS: The prevalence of life dissatisfaction was estimated to be 5.0% among adults. People with one, two, and three health risk factors were, respectively, 2.2 (95% CI: 2.0-2.5), 3.7 (95% CI: 3.2-4.2), and 5.8 (95% CI: 4.6-7.4) times more likely to report life dissatisfaction than those without (P<0.0001 for linear trend). People with one, two, and three or more chronic illnesses were, respectively, 1.8 (95% CI: 1.7-2.0), 3.6 (95% CI: 3.2-4.0), and 5.0 (95% CI: 4.4-5.7) times more likely to report life dissatisfaction than those without (P<0.0001). After adjustment for self-rated health and other potential confounding variables, the associations were attenuated but remained significant for the number of health risk factors (P<0.0001 for linear trend) and the number of chronic illnesses (P<0.001). CONCLUSIONS: Clustering of health risk factors or chronic illnesses was associated with life dissatisfaction independently of self-rated health and other established correlates. |
Characteristics of men who have sex with men and women and women who have sex with women and men: results from the 2003 Seattle sex survey
Levin EM , Koopman JS , Aral SO , Holmes KK , Foxman B . Sex Transm Dis 2009 36 (9) 541-6 Men who have sex with both men and women (MSM/W) are second in importance to injection drug users as a source of HIV infection in heterosexual women (WSM) in the United States.1 Of the women who contracted HIV through heterosexual contact in 2004, 15% reported sex with MSM/W as their only risk factor2; this is probably an underestimate, as between 33% and 75% of MSM/W do not disclose to female partners that they have sex with men.3,4 | MSM/W bridge 2 populations: Men who have sex with men (MSM), a population with high prevalence of sexually-transmitted infections (STI’s), including HIV, and heterosexual females who have lower STI prevalence. MSM/W also report higher numbers of sex partners, more casual sex partners, and less frequent condom use than other groups, increasing their STI risk.4 Women who have sex with women and men (WSW/M) act as a sexual bridge between heterosexual men (MSW) and women who have sex with women (WSW)—a group with relatively low STI prevalence. The impact of MSM/W bridging between MSM and WSM on the AIDS epidemic in the United States has been explored using risk models.1,5 The resulting probabilistic risk assessments suggest that even a small number of MSM/W bridging could profoundly effect HIV transmission, and presumably, other STI, at the population level if MSM/W have a central role in connecting multiple sexual networks that would otherwise remain separate as demonstrated by Hightow et al.5,6 Most data on MSM/W and WSW/M come from select populations, such as persons with AIDS, persons at gay bars or sexual pick-up areas, or patients in STI clinics; there are few general population estimates of MSM/W and WSW/M prevalence. We describe the prevalence of and sexual behaviors among MSM/W and WSW/M identified from participants in a random digit dialing (RDD) survey of individuals aged between 18 and 39. |
Hepatitis A seroprevalence and risk factors among homeless adults in San Francisco: should homelessness be included in the risk-based strategy for vaccination?
Hennessey KA , Bangsberg DR , Weinbaum C , Hahn JA . Public Health Rep 2009 124 (6) 813-7 OBJECTIVES: Homeless adults have an increased risk of infectious diseases due to sexual and drug-related behaviors and substandard living conditions. We investigated the prevalence and risk factors for presence of hepatitis A virus (HAV) antibodies among homeless and marginally housed adults. METHODS: We analyzed serologic and questionnaire data from a study of marginally housed and homeless adults in San Francisco from April 1999 to March 2000. We tested seroprevalance for total antibodies to HAV (anti-HAV) and analyzed data using Chi-square tests and logistic regression. RESULTS: Of the 1,138 adults in the study, 52% were anti-HAV positive. The anti-HAV prevalence in this study population was 58% higher than the expected prevalence based on age-specific prevalence rates from the general population. Number of years of homelessness (< or =1, 2-4, and > or =5 years) was associated with anti-HAV prevalence (46%, 50%, and 61%, respectively, p < 0.001). We found other differences in anti-HAV prevalence (p < 0.05) for ever having injected drugs (63% vs. 42% for non-injectors), being foreign-born (75% vs. 51% among U.S.-born), race/ethnicity (72%, 53%, and 45% for Hispanic, white, and black people, respectively), and increasing age (38%, 49%, and 62% among those aged <35, 35-45, and >45 years, respectively). These variables all remained significant in a multivariate model. CONCLUSIONS: We found overall anti-HAV prevalence elevated in this San Francisco homeless population compared with the general U.S. population. These data show that anti-HAV was associated with homelessness independent of other known risk factors, such as being foreign-born, race/ethnicity, and injection drug use. This increase indicates an excess risk of HAV infection and the potential need to offer hepatitis A vaccination as part of homeless services. |
Pseudo-outbreak of "Mycobacterium paraffinicum" infection and/or colonization in a tertiary care medical center
Wang SH , Pancholi P , Stevenson K , Yakrus MA , Butler WR , Schlesinger LS , Mangino JE . Infect Control Hosp Epidemiol 2009 30 (9) 848-53 OBJECTIVE: To investigate a pseudo-outbreak of "Mycobacterium paraffinicum" (unofficial taxon) infection and/or colonization, using isolates recovered from clinical and environmental specimens. DESIGN: Outbreak investigation. SETTING: University-affiliated, tertiary-care hospital. METHODS: M. paraffinicum, a slow-growing, nontuberculous species of mycobacteria, was recovered from 21 patients and an ice machine on a single patient care unit over a 2.5-year period. The clinical, epidemiological, and environmental investigation of this pseudo-outbreak is described. RESULTS: Twenty-one patients with pulmonary symptoms and possible risk factors for tuberculosis were admitted to inpatient rooms that provided airborne isolation conditions in 2 adjacent hospital buildings. In addition, 1 outpatient had induced sputum cultured for mycobacteria in the pulmonary function laboratory. Of the samples obtained from these 21 patients, 26 isolates from respiratory samples and 1 isolate from a stool sample were identified as M. paraffinicum. Environmental isolates obtained from an ice machine in the patient care unit where the majority of the patients were admitted were also identified as M. paraffinicum. CONCLUSIONS: An epidemiological investigation that used molecular tools confirmed the suspicion of a pseudo-outbreak of M. paraffinicum infection and/or colonization. The hospital water system was identified as the source of contamination. |
Comparison of risk factors for recovery of Acinetobacter baumannii during outbreaks at two Kentucky hospitals, 2006
Beavers SF , Blossom DB , Wiemken TL , Kawaoka KY , Wong A , Goss L , McCormick MI , Thoroughman D , Srinivasan A . Public Health Rep 2009 124 (6) 868-74 OBJECTIVES: Acinetobacter baumannii (A. baumannii) is a well-described cause of nosocomial outbreaks and can be highly resistant to antimicrobials. We investigated A. baumannii outbreaks at two Kentucky hospitals to find risk factors for Acinetobacter acquisition in hospitalized patients. METHODS: We performed case-control studies at both hospitals. We defined a case as a clinical culture growing A. baumannii from a patient from August 1 to October 31, 2006 (Hospital A), or April 1 to October 31, 2006 (Hospital B). RESULTS: Twenty-nine cases were identified at Hospital A and 72 cases were identified at Hospital B. The median case patient age was 42 years in Hospital A and 46 years in Hospital B. The majority of positive cultures were from sputum (Hospital A, 51.7%; Hospital B, 62.5%). The majority of case patients had multidrug-resistant A. baumannii (Hospital A, 75.9%; Hospital B, 70.8%). Using logistic regression, controlling for age and admitting location, mechanical ventilation (Hospital A odds ratio [OR] = 21.6; 95% confidence interval [CI] 3.5, 265.9; Hospital B OR = 4.5, 95% CI 1.9, 11.1) was associated with A. baumannii recovery. Presence of a nonsurgical wound (OR = 6.6, 95% CI 1.2, 50.8) was associated with recovery of A. baumannii at Hospital A. CONCLUSIONS: We identified similar patient characteristics and risk factors for A. baumannii acquisition at both hospitals. Our findings necessitate the importance of review of infection control procedures related to respiratory therapy and wound care. |
Oral rotavirus vaccines: how well will they work where they are needed most?
Patel M , Shane AL , Parashar UD , Jiang B , Gentsch JR , Glass RI . J Infect Dis 2009 200 S39-48 Rotavirus vaccines hold promise to decrease the burden of severe diarrhea in the poorest countries, where 85% of deaths due to rotavirus occur. However, the potency of live oral vaccines is lower in these challenging settings than in middle- and upper-income countries. Many hypotheses have been suggested to explain these differences that could provide clues to improve the ultimate success of these novel vaccines. Although introduction today of even moderately effective vaccines will decrease the morbidity and mortality associated with rotavirus in low-income settings, research is urgently needed to understand why these differences in efficacy occur and what could be done to improve vaccine performance to maximize the life-saving benefits of vaccination. |
Projected impact of the new rotavirus vaccination program on hospitalizations for gastroenteritis and rotavirus disease among US children <5 years of age during 2006-2015
Curns AT , Coffin F , Glasser JW , Glass RI , Parashar UD . J Infect Dis 2009 200 S49-56 BACKGROUND: Rotavirus causes approximately one-third to one-half (55,000-70,000 hospitalizations per year) of hospitalizations for acute gastroenteritis (AGE) among US children <5 years of age. We forecasted the potential reduction in the number of hospitalizations for rotavirus disease and AGE in US children during 2006-2015 as a result of the new rotavirus vaccine introduced in 2006. METHODS: The mean number of hospitalizations for AGE by calendar month among US children was determined using the National Hospital Discharge Survey from the period 1993-2005. From these baseline prevaccine estimates, we forecasted the effect of vaccine in reducing the number of hospitalizations for rotavirus disease and AGE during 2006-2015 with use of estimates of vaccine effectiveness and uptake. RESULTS: During 2006-2015, approximately 313,000 (45%) of an estimated 703,190 hospitalizations for rotavirus disease would be directly prevented by vaccination. A significant reduction in the number of hospitalizations for AGE should be detectable among infants aged 0-11 months during the first quarter of 2009, followed by children aged 12-23 months during 2010, and all children <5 years of age during 2011. CONCLUSIONS: Vaccination is expected to substantially reduce the health burden of hospitalizations for rotavirus disease among US children during 2006-2015, and the impact of vaccination based on direct protective effects alone was expected to first occur for hospitalizations for AGE among infants during winter 2009. |
Real-time surveillance to assess risk of intussusception and other adverse events after pentavalent, bovine-derived rotavirus vaccine
Belongia EA , Irving SA , Shui IM , Kulldorff M , Lewis E , Yin R , Lieu TA , Weintraub E , Yih WK , Li R , Baggs J , The Vaccine Safety Datalink Investigation Group . Pediatr Infect Dis J 2009 29 (1) 1-5 BACKGROUND: A pentavalent, bovine-derived rotavirus vaccine (RotaTeq, Merck) was licensed in 2006 for use in infants. A previously licensed rotavirus vaccine was withdrawn due to elevated risk of intussusception. We prospectively evaluated the risk of intussusception and other pre-specified adverse events among RotaTeq recipients in the Vaccine Safety Datalink. METHODS: The exposed population included children from age 4 to 48 weeks who received RotaTeq between May 2006 and May 2008. Adverse events over the subsequent 30 days were ascertained from inpatient, outpatient, and emergency department files; cases of intussusception were validated by medical record review. An adaptation of sequential probability ratio testing was employed to compare the cumulative number of observed and expected adverse events on a weekly basis, and a "signal" was generated if the log-likelihood ratio reached a predetermined threshold. This allowed near real-time monitoring to detect selected adverse events. The expected number of cases of intussusception was determined from historical rates in the VSD population. RESULTS: There were 207,621 doses of RotaTeq administered to the study population; 42% were first doses. Five children had computerized diagnosis codes for intussusception, and 6.75 cases were expected based on historical rates (relative risk = 0.74). No elevation in risk was identified for intussusception or any other adverse event. Two of five children with suspected intussusception based on diagnosis codes met the case criteria after medical record review. CONCLUSIONS: This study illustrates the feasibility of rapid vaccine safety assessment and provides additional evidence that RotaTeq is not associated with an increased risk of intussusception. |
Underestimates of intussusception rates among US infants based on inpatient discharge data: implications for monitoring the safety of rotavirus vaccines
Cortese MM , Staat MA , Weinberg GA , Edwards K , Rice MA , Szilagyi PG , Hall CB , Payne DC , Parashar UD . J Infect Dis 2009 200 S264-70 BACKGROUND: Because a previous rotavirus vaccine was associated with intussusception, new rotavirus vaccines are monitored postlicensure for any such association. Accurate background intussusception rates are needed to determine whether the number of cases observed after vaccination exceeds that expected by chance. Previously, intussusception rates were obtained from inpatient discharge databases. We sought to determine the rate of intussusception among infants managed only with short-stay or emergency department care. METHODS: Intussusception cases occurring in infants were identified retrospectively at 3 children's hospitals from January 2001 through March 2006, a period without rotavirus vaccine use, by a search of discharge, billing, and radiology databases for International Classification of Diseases, Ninth Revision, Clinical Modification code 560.0 (intussusception) and procedure codes and by review of medical records. RESULTS: Of 156 infants with intussusception fulfilling Brighton level 1 criteria, 81 (52%) were billed as inpatients, 68 (44%) as short-stay patients, and 7 (4%) as emergency department patients only. The use of only inpatients assigned code 560.0 underestimated the total number of level 1 cases at the hospitals by 44%. The mean annual intussusception rate for the hospitals' catchment counties was 49.3 cases per 100,000 live births (inpatient cases: 27.1 cases per 100,000 live births; short-stay or emergency department cases: 22.3 cases per 100,000 live births). CONCLUSIONS: Intussusception rates based solely on inpatient discharge databases could underestimate the true incidence of level 1 intussusception by >40%. Background rates used for assessment of risk after vaccination should account for cases managed only with short-stay or emergency department care. |
Vaccinating adolescents--new evidence of challenges and opportunities
Rodewald LE , Orenstein WA . J Adolesc Health 2009 45 (5) 427-9 An incompletely vaccinated toddler has several well-child care visits to catch up on immunizations, and, failing these annual vaccination opportunities, school immunization laws serve as enforced reminders to become immunized. | In contrast, an incompletely vaccinated adolescent will become a young adult and enter a stage of life in which routine preventive visits generally do not occur. Compounding matters, financially vulnerable young adults lose their entitlement to free vaccines once they are 19 years old and cross the age for inclusion to the Vaccines for Children (VFC) program. | From a purely programmatic viewpoint, vaccinating at as young an age as possible has the advantage of longer catch-up time before the ages of heightened risk of exposure to vaccine-preventable infections. This is one reason that the adolescent platform for vaccination is recommended for 11- and 12-year-olds. Provided that the duration of protection afforded by vaccination lasts through the ages of greatest risk, it is reasonable to concentrate vaccination at this young age. |
Varicella-zoster virus subunit vaccine
Vafai A . Open Vaccine J 2009 2 (1) 17-27 Varicella-zoster virus (VZV) causes chickenpox (Varicella) in children and shingles (Zoster) in elderly and immunosuppressed individuals. An attenuated VZV vaccine has been approved for general immunization to prevent varicella and zoster in the United States. Although this vaccine provides a high degree of protection against virus infection, the virus becomes latent in dorsal root ganglia and will reactivate to produce zoster. Therefore, there is a need for developing additional VZV vaccines that are capable of eliciting immune response to the virus but will not establish viral latency. Our studies have been focused on the development of a truncated secretory VZV glycoprotein (VZVgE) subunit vaccine. The results from our studies have shown that the VZV subunit vaccine: (1) elicits the induction of neutralizing antibodies in animals as well as in humans; and (2) stimulates the induction of VZVgE-specific antibodies in VZV-seropositive human mononuclear cells. Such a VZV glycoprotein antigen, therefore, may have the potential to be used as a candidate VZV glycoprotein subunit vaccine for prevention of primary VZV infection (Varicella) or boosting immune response against VZV reactivation (Zoster) in adults, the elderly and immunosuppressed individuals. copyright Abbas Wafai; Licensee Bentham Open. |
Viscerotropic disease following yellow fever vaccination in Peru
Whittembury A , Ramirez G , Hernandez H , Ropero AM , Waterman S , Ticona M , Brinton M , Uchuya J , Gershman M , Toledo W , Staples E , Campos C , Martinez M , Chang GJ , Cabezas C , Lanciotti R , Zaki S , Montgomery JM , Monath T , Hayes E . Vaccine 2009 27 (43) 5974-81 Five suspected cases of yellow fever vaccine-associated viscerotropic disease (YEL-AVD) clustered in space and time following a vaccination campaign in Ica, Peru in 2007. All five people received the same lot of 17DD live attenuated yellow fever vaccine before their illness; four of the five died of confirmed YEL-AVD. The surviving case was classified as probable YEL-AVD. Intensive investigation yielded no abnormalities of the implicated vaccine lot and no common risk factors. This is the first described space-time cluster of yellow fever viscerotropic disease involving more than two cases. Mass yellow fever vaccination should be avoided in areas that present extremely low risk of yellow fever. |
Adolescent immunization delivery in school-based health centers: a national survey
Daley MF , Curtis CR , Pyrzanowski J , Barrow J , Benton K , Abrams L , Federico S , Juszczak L , Melinkovich P , Crane LA , Kempe A . J Adolesc Health 2009 45 (5) 445-52 PURPOSE: Vaccinating adolescents in a variety of settings may be needed to achieve high vaccination coverage. School-based health centers (SBHCs) provide a wide range of health services, but little is known about immunization delivery in SBHCs. The objective of this investigation was to assess, in a national random sample of SBHCs, adolescent immunization practices and perceived barriers to vaccination. METHODS: One thousand SBHCs were randomly selected from a national database. Surveys were conducted between November 2007 and March 2008 by Internet and standard mail. RESULTS: Of 815 survey-eligible SBHCs, 521 (64%) responded. Of the SBHCs, 84% reported vaccinating adolescents, with most offering tetanus-diphtheria-acellular pertussis, meningococcal conjugate, and human papillomavirus vaccines. Among SBHCs that vaccinated adolescents, 96% vaccinated Medicaid-insured and 98% vaccinated uninsured students. Although 93% of vaccinating SBHCs participated in the Vaccines for Children program, only 39% billed private insurance for vaccines given. A total of 69% used an electronic database or registry to track vaccines given, and 83% sent reminders to adolescents and/or their parents if immunizations were needed. For SBHCs that did not offer vaccines, difficulty billing private insurance was the most frequently cited barrier to vaccination. CONCLUSIONS: Most SBHCs appear to be fully involved in immunization delivery to adolescents, offering newly recommended vaccines and performing interventions such as reminder/recall to improve immunization rates. Although the number of SBHCs is relatively small, with roughly 2000 nationally, SBHCs appear to be an important vaccination resource, particularly for low income and uninsured adolescents who may have more limited access to vaccination elsewhere. |
Assessing the effectiveness and public health impact of rotavirus vaccines after introduction in immunization programs
Patel MM , Parashar UD . J Infect Dis 2009 200 S291-9 Two new vaccines against severe rotavirus gastroenteritis that have high efficacy in middle- and high-income countries have recently been licensed in many countries worldwide. Clinical trials in low-income countries in Africa and Asia are ongoing. Experience gained through studies of natural rotavirus infection and the clinical trials for the current and previous rotavirus vaccines indicate that, as countries begin to introduce these newly approved vaccines into routine childhood immunization programs, monitoring their performance in real world settings should be a high priority. Key epidemiological considerations in the postlicensure period include (1) how the vaccine will perform against severe rotavirus disease under routine public health use; (2) how routine vaccination will impact the epidemiology of disease with regard to the burden of severe disease and death, age distribution of cases, seasonality, and serotype distribution; (3) whether vaccination will have a sufficient impact on transmission to reduce disease burden in unvaccinated age groups; and (4) whether vaccine will confer protection through the first 3 years of life, when most severe disease and mortality associated with rotavirus occur. Monitoring of impact with focus on these public health considerations will allow parents, health care providers, and decision makers to appreciate the health benefits of vaccination in reducing the burden of severe rotavirus disease. It will also allow assessment of the effectiveness of rotavirus vaccines in programmatic use and the need for modifying vaccination schedules or vaccine formulations to enhance the performance of immunization. In this article, we review data for the protective efficacy of the 2 new rotavirus vaccines, with emphasis on issues particularly important for consideration as these vaccines are introduced in routine infant immunization programs. |
Global rotavirus surveillance: determining the need and measuring the impact of rotavirus vaccines
Widdowson MA , Steele D , Vojdani J , Wecker J , Parashar U . J Infect Dis 2009 200 S1-8 Rotavirus remains the most common cause of severe childhood diarrhea worldwide and of diarrheal mortality in poor countries. In 2003, the GAVI Alliance launched the Rotavirus Vaccine Program and the Accelerated Development and Introduction Plan to close the gap of access to rotavirus vaccines in industrialized and developing countries by generating data on rotavirus disease burden, projected impact, and cost-effectiveness of vaccination and by conducting clinical trials of existing vaccines in impoverished settings. By the end of 2008, rotavirus vaccines were licensed in >100 countries, although only 17 countries have introduced routine rotavirus vaccination. Increased uptake of the vaccine by countries with the highest childhood mortality will depend in part on a solid evidence base of estimated burden and cost of rotavirus illness. Since 2001, regional surveillance networks worldwide have generated burden and strain data from 196 sites in 59 countries. Among children aged <5 years who are hospitalized for severe diarrhea in different regions of the world, a regional median of 39% (range by country, 20%-73%) test positive for rotavirus. Rotavirus vaccines are a cost-effective intervention and may be cost saving with a GAVI Alliance subsidy from the health care perspective. Punctual vaccination and high coverage of populations at highest risk of mortality will maximize the impact of vaccination. Surveillance platforms will allow measurement of the rapid impact of rotavirus vaccine introduction on the heavy burden of rotavirus on child health worldwide. |
How much could rotavirus vaccines reduce diarrhea-associated mortality in northern Ghana? A model to assess impact
Arvay ML , Curns AT , Terp S , Armah G , Wontuo P , Parashar UD , Binka F , Glass RI , Widdowson MA . J Infect Dis 2009 200 S85-91 BACKGROUND: Effective rotavirus vaccines could substantially reduce the approximately 500,000 deaths due to rotavirus disease per year worldwide, although the impact will depend on vaccine effectiveness, timing of administration, and coverage. We modeled vaccine impact on rotavirus-associated mortality in rural Ghana. METHODS: All deaths due to acute diarrhea among children during 1998-2004 in the Kassena-Nankana District of Ghana were identified, and the number of deaths due to rotavirus disease was estimated using hospital laboratory surveillance data. Assuming rotavirus vaccine would be included in the current Expanded Program on Immunization schedule, we estimated the reduction in rotavirus-associated mortality with use of the current coverage and timing of diphtheria, tetanus, and pertussis vaccine administration and various age-restricted schedules. RESULTS: Of the 381 deaths due to diarrhea, 131 (34%) were estimated to be caused by rotavirus infection. On the basis of current diphtheria, tetanus, and pertussis vaccine coverage and timing, a 90% efficacious 3-dose rotavirus vaccine would prevent 70% of deaths due to rotavirus infection if administered without age restrictions, 53% if only initiated among children <12 weeks of age, and 52% if the course also was completed by 32 weeks of age. CONCLUSIONS: Rotavirus vaccine has the potential to substantially reduce rotavirus-associated mortality in rural Ghana. Although timely vaccination should be encouraged, extending the current age recommendation for initiation of rotavirus vaccination could increase the coverage and impact of vaccination. |
Using an immunization information system to improve accountability for vaccines distributed through the Vaccines for Children program in New York City, 2005-2008
Metroka AE , Hansen MA , Papadouka V , Zucker JR . J Public Health Manag Pract 2009 15 (5) E13-21 BACKGROUND: As new, higher-priced vaccines are added to the immunization schedule, Vaccines for Children (VFC) program costs are increasing and attention has been focused on strengthening accountability. In New York City, the VFC program distributes publicly purchased vaccines, worth nearly $117 million annually, to more than 1,500 enrolled facilities to immunize eligible children. In 2006, we changed our policy of requiring facilities to account for administration of VFC vaccines by submitting self-reported, aggregate doses administered reports (DARs) when ordering VFC vaccines to using DARs generated from our immunization information system (IIS), the Citywide Immunization Registry (CIR). New York City providers have been required to report immunizations to the CIR since 1997. OBJECTIVES: To increase VFC accountability and reporting to the CIR by linking vaccine ordering and distribution to reporting of doses administered. METHODS: We matched all VFC facilities to those in the CIR. Using CIR and VFC data, we calculated a CIR-generated DAR percentage for each facility by dividing doses reported by doses distributed. We informed facilities that their CIR-generated DAR must be more than 90 percent or their VFC vaccine orders may be reduced. RESULTS: After the policy change, doses reported to the CIR for children younger than 8 years increased 71 percent, and the percentage of doses distributed that were reported as administered to eligible children increased from 40 to 67. Few facilities protested; none dropped out of VFC. CONCLUSIONS: Replacing self-reported DARs with IIS-generated DARs improved VFC accountability and increased reporting to the IIS. Immunization programs nationwide may achieve similar success using this strategy. |
Stability of varicella-zoster virus and herpes simplex virus IgG monoclonal antibodies
Hart J , Miller C , Tang X , Vafai A . J Immunoassay Immunochem 2009 30 (2) 180-5 The stability of 3 monoclonal antibodies was analyzed at various temperatures and freeze/thaw cycles. Two varicella-zoster virus (VZV) IgGs (mAb 4F9 and mAb g62) and 1 herpes simplex virus 1 (HSV-1 mAb 1D4) were selected for these studies. IgGs were either incubated at various temperatures (25 degrees C, 37 degrees C, 45 degrees C, and 60 degrees C) for different periods of time (0 to 9 weeks) or processed for several freeze/thaw cycles. The reactivities of mAbs 4F9 (IgG1), g62 (IgG1) and 1D4 (IgG2b) were tested by indirect immunofluorescence assay (IFA). The results indicated that: (1) all three mAbs were stable at 25 degrees C and 37 degrees C for 9 weeks; (2) although the reactivities of mAbs g62 and 1D4 were diminished after 5 weeks, mAb 4F9 was stable at 45 degrees C for 9 weeks; and (3) all 3 IgGs lost reactivity after overnight incubation at 60 degrees C. In addition, the results showed that the reactivity of mAbs 4F9, g62 and 1D4 was not diminished after 12 freeze/thaw cycles. |
West Nile virus detection in nonvascular feathers from avian carcasses
Nemeth NM , Young GR , Burkhalter KL , Brault AC , Reisen WK , Komar N . J Vet Diagn Invest 2009 21 (5) 616-22 West Nile virus (WNV) is a public health threat and has caused the death of thousands of North American birds. As such, surveillance for WNV has been ongoing, utilizing numerous biological specimens and testing methods. Nonvascular (i.e., fully grown) feathers would provide a simple method of collection from either dead or live birds of all ages and molt cycles, with presumably less biosafety risk compared with other specimen types, including feather pulp. The current study evaluates WNV detection in nonvascular feathers removed from naturally infected avian carcasses of several species groups. Feathers of corvid passeriforms had the highest sensitivity of detection (64%), followed by noncorvid passeriforms (43%), columbiforms (33%), and falconiforms (31%). Storing feathers for 1 year at -20 degrees C or at ambient room temperature resulted in detection rates of infectious WNV of 16% and zero, respectively, but had no effect on detection rates of WNV RNA in a subset of matched feather pairs (47% for both storage temperatures). The efficacy of WNV detection in nonvascular feathers is greatly enhanced by testing multiple feathers. The advantages of using nonvascular feathers over other tissues may outweigh the relatively low detectability of WNV RNA in certain situations such as remote areas lacking resources for acquiring other types of samples or maintaining the cold chain. |
Adaptation and evaluation of the bottle assay for monitoring insecticide resistance in disease vector mosquitoes in the Peruvian Amazon
Zamora Perea E , Balta Leon R , Palomino Salcedo M , Brogdon WG , Devine GJ . Malar J 2009 8 208 BACKGROUND: The purpose of this study was to establish whether the "bottle assay", a tool for monitoring insecticide resistance in mosquitoes, can complement and augment the capabilities of the established WHO assay, particularly in resource-poor, logistically challenging environments. METHODS: Laboratory reared Aedes aegypti and field collected Anopheles darlingi and Anopheles albimanus were used to assess the suitability of locally sourced solvents and formulated insecticides for use with the bottle assay. Using these adapted protocols, the ability of the bottle assay and the WHO assay to discriminate between deltamethrin-resistant Anopheles albimanus populations was compared. The diagnostic dose of deltamethrin that would identify resistance in currently susceptible populations of An. darlingi and Ae. aegypti was defined. The robustness of the bottle assay during a surveillance exercise in the Amazon was assessed. RESULTS: The bottle assay (using technical or formulated material) and the WHO assay were equally able to differentiate deltamethrin-resistant and susceptible An. albimanus populations. A diagnostic dose of 10 microg a.i./bottle was identified as the most sensitive discriminating dose for characterizing resistance in An. darlingi and Ae. aegypti. Treated bottles, prepared using locally sourced solvents and insecticide formulations, can be stored for > 14 days and used three times. Bottles can be stored and transported under local conditions and field-assays can be completed in a single evening. CONCLUSION: The flexible and portable nature of the bottle assay and the ready availability of its components make it a potentially robust and useful tool for monitoring insecticide resistance and efficacy in remote areas that require minimal cost tools. |
Cellular immune responses to severe acute respiratory syndrome coronavirus (SARS-CoV) infection in senescent BALB/c mice: CD4+ T cells are important in control of SARS-CoV infection
Chen J , Lau YF , Lamirande EW , Paddock CD , Bartlett JH , Zaki SR , Subbarao K . J Virol 2009 84 (3) 1289-301 We characterized the cellular immune response to SARS coronavirus (SARS-CoV) infection in 12-14 month old (m/o) BALB/c mice, a model that mimics features of the human disease. Following intranasal administration, the virus replicated in the lungs with peak titers on day (d) 2 post-infection. Enhanced production of cytokines (TNFalpha, IL-6) and chemokines (CXCL10, CCL2, CCL3, CCL5) correlated with migration of NK cells, macrophages and plasmacytoid DC (pDC) into the lungs. By d 7, histopathologic evidence of pneumonitis was seen in the lungs when viral clearance occurred. At this time, a second wave of enhanced production of cytokines (TNFalpha, IL-6, IFNgamma, IL-2, IL-5), chemokines (CXCL9, CXCL10, CCL2, CCL3, CCL5) and receptors (CXCR3, CCR2, CCR5), was detected in the lungs associated with an influx of T lymphocytes. Depletion of CD8(+) T cells at the time of infection did not affect viral replication or clearance. However, depletion of CD4(+) T cells resulted in an enhanced immune-mediated interstitial pneumonitis and delayed clearance of SARS-CoV from the lungs, associated with reduced neutralizing antibody and cytokine production and reduced pulmonary recruitment of lymphocytes. Innate defense mechanisms are able to control SARS-CoV infection in the absence of CD4(+) and CD8(+) T cells and antibodies. Our findings provide new insights into the pathogenesis of SARS, demonstrating the important role of CD4(+) but not CD8(+) T cells in primary SARS-CoV infection in this model. |
Comparison of human fetal liver, umbilical cord blood, and adult blood hematopoietic stem cell engraftment in NOD-scid/gammac-/-, Balb/c-Rag1-/-gammac-/-, and C.B-17-scid/bg immunodeficient mice
Lepus CM , Gibson TF , Gerber SA , Kawikova I , Szczepanik M , Hossain J , Ablamunits V , Kirkiles-Smith N , Herold KC , Donis RO , Bothwell AL , Pober JS , Harding MJ . Hum Immunol 2009 70 (10) 790-802 Immunodeficient mice bearing components of a human immune system present a novel approach for studying human immune responses. We investigated the number, phenotype, developmental kinetics, and function of developing human immune cells following transfer of CD34(+) hematopoietic stem cell (HSC) preparations originating from second trimester human fetal liver (HFL), umbilical cord blood (UCB), or granulocyte colony-stimulating factor-mobilized adult blood (G-CSF-AB) delivered via intrahepatic injection into sublethally irradiated neonatal NOD-scid/gammac(-/-), Balb/c-Rag1(-/-)gammac(-/-), and C.B-17-scid/bg mice. HFL and UCB HSC provided the greatest number and breadth of developing cells. NOD-scid/gammac(-/-) and Balb/c-Rag1(-/-)gammac(-/-) harbored human B and dendritic cells as well as human platelets in peripheral blood, whereas NOD-scid/gammac(-/-) mice harbored higher levels of human T cells. NOD-scid/gammac(-/-) mice engrafted with HFL CD34(+) HSC demonstrated human immunological competence evidenced by white pulp expansion and increases in total human immunoglobulin following immunization with T-dependent antigens and delayed-type hypersensitivity-infiltrating leukocytes in response to antigenic challenge. In conclusion, we describe an encouraging base system for studying human hematopoietic lineage development and function utilizing human HFL or UCB HSC-engrafted NOD-scid/gammac(-/-) mice that is well suited for future studies toward the development of a fully competent humanized mouse model. |
Comparison of lavage and swabs for the collection of genital ulcer specimens to measure HIV RNA shedding
Paz-Bailey G , Sternberg M , Lewis DA , Cutler E , Vos M , Ballard R , Puren A . J Clin Virol 2009 46 (2) 165-8 BACKGROUND: The optimum collection procedure for the evaluation of HIV-1 burden in ulcer secretions has not been well defined. OBJECTIVES: The objective of this study was to compare ulcer swabs and ulcer lavages for the detection and quantitation of HIV-1 RNA in genital ulcers. STUDY DESIGN: A convenience sample of the first 84 HIV-positive participants in a randomized double blind placebo controlled trial of acyclovir episodic treatment among men with genital ulcer disease were included in this evaluation. At baseline, participants were screened for HIV, syphilis and HSV-2 by serology and for ulcer etiology by PCR. Ulcer specimens were collected by using (1) a non-traumatic washing procedure with 10ml of PBS, and (2) sterile dry swabs. Ulcer samples were tested with HIV-1 Amplicor 1.5 Ultra Sensitive Assay with a lower threshold of 50 copies/ml. RESULTS: Of ulcer samples 35 (41.7%) had HIV detected by ulcer lavage and 32 (38.1%) by swabs (p=0.68). Overall, 45 (53.6%) were positive by one or both methods. The overall proportion of agreement was 73% (61/84). The chance-corrected proportion of agreement was 0.46 (95% CI: 0.26, 0.65) as estimated by the Kappa statistic. The log mean viral load from lavages (1.49log(10) copies/ml, 95% CI: 1.17-1.81) did not differ significantly from that of swabs (1.41log(10) copies/ml, 95% CI: 1.16-1.71) (p=0.29) with a mean difference of 0.08log copies/ml (SD 0.96). CONCLUSION: Ulcer lavage and ulcer swab performed in moderate agreement in the detection and quantitation of HIV RNA from ulcer specimens. |
GC Content-Based Pan-Pox Universal PCR Assays for Poxvirus Detection
Li Y , Meyer H , Zhao H , Damon IK . J Clin Microbiol 2009 48 (1) 268-76 Chordopoxviruses of the subfamily Chordopoxvirinae, family Poxviridae, infect vertebrates and consist of at least eight genera with broad host ranges. For most chordopoxviruses, the number of viral genes and their relative order is highly conserved in the central region. The G+C content of chordopoxvirus genomes, however, evolved into two distinct types: those with genome G+C content of more than 60% and those with a content of less than 40% of G+C. Two standard PCR assays were developed to identify chordopoxviruses based on whether the target virus has a low or high G+C content. In design of the assays, the genus Avipoxvirus, which encodes major rearrangements of gene clusters, was excluded. These pan_pox assays amplify DNA from more than 150 different isolates and strains, including from primary clinical materials, from all seven targeted genera of chordopoxviruses and four unclassified new poxvirus species. The pan_pox assays represent an important advance for the screening and diagnosis of human and animal poxvirus infections, and the technology used is accessible to many laboratories worldwide. |
Interlaboratory evaluation of a standardized inductively coupled plasma mass spectrometry method for the determination of trace beryllium in air filter samples
Ashley K , Brisson MJ , Howe AM , Bartley DL . J Occup Environ Hyg 2009 6 (12) 745-50 A collaborative interlaboratory evaluation of a newly standardized inductively coupled plasma mass spectrometry (ICP-MS) method for determining trace beryllium in workplace air samples was carried out toward fulfillment of method validation requirements for ASTM International voluntary consensus standard test methods. The interlaboratory study (ILS) was performed in accordance with an applicable ASTM International standard practice, ASTM E691, which describes statistical procedures for investigating interlaboratory precision. Uncertainty was also estimated in accordance with ASTM D7440, which applies the International Organization for Standardization Guide to the Expression of Uncertainty in Measurement to air quality measurements. Performance evaluation materials (PEMs) used consisted of 37 mm diameter mixed cellulose ester filters that were spiked with beryllium at levels of 0.025 (low loading), 0.5 (medium loading), and 10 (high loading) microg Be/filter; these spiked filters were prepared by a contract laboratory. Participating laboratories were recruited from a pool of over 50 invitees; ultimately, 20 laboratories from Europe, North America, and Asia submitted ILS results. Triplicates of each PEM (blanks plus the three different loading levels) were conveyed to each volunteer laboratory, along with a copy of the draft standard test method that each participant was asked to follow; spiking levels were unknown to the participants. The laboratories were requested to prepare the PEMs by one of three sample preparation procedures (hotplate or microwave digestion or hotblock extraction) that were described in the draft standard. Participants were then asked to analyze aliquots of the prepared samples by ICP-MS and to report their data in units of mu g Be/filter sample. Interlaboratory precision estimates from participating laboratories, computed in accordance with ASTM E691, were 0.165, 0.108, and 0.151 (relative standard deviation) for the PEMs spiked at 0.025, 0.5, and 10 microg Be/filter, respectively. Overall recoveries were 93.2%, 102%, and 80.6% for the low, medium, and high beryllium loadings, respectively. Expanded uncertainty estimates for interlaboratory analysis of low, medium, and high beryllium loadings, calculated in accordance with ASTM D7440, were 18.8%, 19.8%, and 24.4%, respectively. These figures of merit support promulgation of the analytical procedure as an ASTM International standard test method, ASTM D7439. |
Long-term speech and language developmental issues among children with Duarte galactosemia
Powell KK , Braun KV , Singh RH , Shapira SK , Olney RS , Yeargin-Allsopp M . Genet Med 2009 11 (12) 874-9 PURPOSE: There is limited information on long-term outcomes among children with Duarte galactosemia and controversy about treatment of this potentially benign condition. This study examined developmental disabilities and issues that required special education services within a population-based sample of children with Duarte galactosemia. METHODS: Children born between 1988 and 2001 who were diagnosed with Duarte galactosemia and resided in the five-county metropolitan Atlanta area at birth and from 3 to 10 years of age were linked to the (1) Metropolitan Atlanta Developmental Disabilities Surveillance Program, an ongoing, population-based surveillance system for selected developmental disabilities and (2) Special Education Database of Metropolitan Atlanta. Special education records were reviewed for children who linked. Clinical genetics records were reviewed to assess laboratory levels at the time of diagnosis and metabolic control during treatment. RESULTS: Of the 59 eligible children, none were found to have intellectual disability, cerebral palsy, hearing loss, vision impairment, or an autism spectrum disorder. However, five, 8.5% of 3 to 10 years or 15.2% of eligible 8 years, were identified as having received special education services, four of whom were confirmed with a speech or language disorder, or were receiving services for speech or language or both compared with 4.5% and 5.9% of children without Duarte galactosemia, respectively. CONCLUSIONS: Despite galactose restriction until 1 year, select developmental issues associated with special education, specifically involving speech and language, have been found among some children with Duarte galactosemia. |
Pandemic influenza and pregnant women: summary of a meeting of experts
Rasmussen SA , Jamieson DJ , Macfarlane K , Cragan JD , Williams J , Henderson Z , Pandemic Influenza Pregnancy Working Group . Am J Public Health 2009 99 S248-54 Pandemic Influenza: Special Considerations for Pregnant Women was a meeting convened by the Centers for Disease Control and Prevention in 2008 to obtain input from experts and key partners regarding clinical management of pregnant women and related public health actions to be taken during a pandemic. Meeting goals were to discuss issues specific to pregnant women, identify gaps in knowledge, and develop a public health approach for pregnant women in the event of a pandemic. The meeting focused on 4 main topics: prophylaxis and treatment with influenza antiviral and other medications, vaccine use, nonpharmaceutical interventions and health care planning, and communications. Participants reviewed the available evidence to guide action in each of these areas and identified areas of critical needs for future research. |
Birth weight and health and developmental outcomes in US children, 1997-2005
Boulet SL , Schieve LA , Boyle CA . Matern Child Health J 2009 15 (7) 836-44 The primary goal of this study was to assess the association between the full birth weight distribution and prevalence of specific developmental disabilities and related measures of health and special education services utilization in US children. Using data from the 1997-2005 National Health Interview Survey (NHIS) Sample Child Core, we identified 87,578 children 3-17 years of age with parent-reported information on birth weight. We estimated the prevalences of DDs (attention-deficit/hyperactivity disorder [ADHD], autism, cerebral palsy, hearing impairment, learning disability without mental retardation, mental retardation, seizures, stuttering/stammering, and other developmental delay) and several indicators of health services utilization within a range of birth weight categories. We calculated odds ratios adjusted for demographic factors (AOR). We observed trends of decreasing disability/indicator prevalence with increasing birth weight up to a plateau. Although associations were strongest for very low birth weight, children with "normal" birth weights of 2,500-2,999 g were more likely than those with birth weights of 3,500-3,999 g to have mental retardation (AOR 1.9 [95% CI: 1.4-2.6]), cerebral palsy (AOR 2.4 [95% CI: 1.5-3.8]), learning disability without mental retardation (AOR 1.2 [95% CI: 1.1-1.4]), ADHD (AOR 1.2 [95% CI: 1.1-1.3]), and other developmental delay (AOR 1.3 [95% CI: 1.1-1.5]) and to receive special education services (AOR 1.3 [95% CI: 1.2-1.5]). While much research has focused on the health and developmental outcomes of low and very low birth weight children, these findings suggest that additional study of a continuous range of birth weights may be warranted. |
Closing the quality gap: promoting evidence-based breastfeeding care in the hospital
Bartick M , Stuebe A , Shealy KR , Walker M , Grummer-Strawn LM . Pediatrics 2009 124 (4) e793-802 Evidence shows that hospital-based practices affect breastfeeding duration and exclusivity throughout the first year of life. However, a 2007 CDC survey of US maternity facilities documented poor adherence with evidence-based practice. Of a possible score of 100 points, the average hospital scored only 63 with great regional disparities. Inappropriate provision and promotion of infant formula were common, despite evidence that such practices reduce breastfeeding success. Twenty-four percent of facilities reported regularly giving non-breast milk supplements to more than half of all healthy, full-term infants. Metrics available for measuring quality of breastfeeding care, range from comprehensive Baby-Friendly Hospital Certification to compliance with individual steps such as the rate of in-hospital exclusive breastfeeding. Other approaches to improving quality of breastfeeding care include (1) education of hospital decision-makers (eg, through publications, seminars, professional organization statements, benchmark reports to hospitals, and national grassroots campaigns), (2) recognition of excellence, such as through Baby-Friendly hospital designation, (3) oversight by accrediting organizations such as the Joint Commission or state hospital authorities, (4) public reporting of indicators of the quality of breastfeeding care, (5) pay-for-performance incentives, in which Medicaid or other third-party payers provide additional financial compensation to individual hospitals that meet certain quality standards, and (6) regional collaboratives, in which staff from different hospitals work together to learn from each other and meet quality improvement goals at their home institutions. Such efforts, as well as strong central leadership, could affect both initiation and duration of breastfeeding, with substantial, lasting benefits for maternal and child health. |
Exposure to the pharmaceutical excipients benzyl alcohol and propylene glycol among critically ill neonates
Shehab N , Lewis CL , Streetman DD , Donn SM . Pediatr Crit Care Med 2009 10 (2) 256-9 OBJECTIVE: To document neonatal exposures to the potentially harmful pharmaceutical excipients benzyl alcohol (BA) and propylene glycol (PG) present in parenteral medications routinely administered in the intensive care unit. DESIGN: Retrospective, observational study. SETTING: Neonatal and pediatric intensive care units of a tertiary care, university hospital. PATIENTS: Randomly selected sample of 170 episodes of exposure to parenteral medications containing BA (n = 88) or PG (n = 82). MEASUREMENTS: We identified all medication sources of BA or PG administered to study neonates during hospitalization, and calculated cumulative doses (mg/kg/day and mg/day) of BA or PG received as a result of exposure to those medications. MAIN RESULTS: We observed a wide range in the cumulative excipient dose received by neonates. Median (range) cumulative dose was 4.5 mg/kg/day (0.6-319.5 mg/kg/day) for BA, and 204.9 mg/kg/day (17.3-9472.7 mg/kg/day) for PG. Patients who received medications via continuous infusion received significantly higher excipient doses than patients who received medications intermittently (p < 0.0001). In this subset of patients, median cumulative excipient doses (BA, 106.3 mg/kg/day and PG, 4554.5 mg/kg/day) were approximately 21 and 180 times the acceptable daily intakes of BA and PG (5 and 25 mg/kg/day), respectively, and exceeded the doses above which toxicity has been reported in infants. No significant correlation between duration of medication administration and cumulative excipient exposure was identified for BA or PG. Midazolam and lorazepam were involved in over two-thirds of BA and PG exposures, respectively. CONCLUSIONS: Critically ill neonates, especially those receiving medications by continuous infusion, are at risk of being exposed to BA and PG at potentially toxic doses during routine medication administration. Given the serious adverse reactions known to be associated with BA and PG, future studies are warranted to determine the clinical consequences associated with this degree of excipient exposure. |
Gestational diabetes mellitus: all Asians are not alike
Chu SY , Abe K , Hall LR , Kim SY , Njoroge T , Qin C . Prev Med 2009 49 265-8 OBJECTIVE: To estimate the prevalence of gestational diabetes mellitus (GDM) prevalence estimates for subgroups of US Asian and Pacific Islander (API) women by using data from 2005 and 2006 birth certificates. METHODS: Using 2005-2006 natality files from states that implemented the revised 2003 US birth certificate, which differentiates between GDM and preexisting diabetes (2005: 12 states; 2006: 19 states), we calculated age-adjusted GDM prevalence estimates for API mothers who delivered singleton infants. RESULTS: Among 3,108,877 births, US APIs had a substantially higher age-adjusted prevalence of GDM (6.3%) than whites (3.8%), blacks (3.5%), or Hispanics (3.6%). Among API subgroups, age-adjusted GDM prevalence varied significantly, from 3.7% among women of Japanese descent to 8.6% among women of Asian Indian descent. Foreign-born APIs had significantly higher GDM rates than US-born APIs except among women of Japanese and Korean ancestry. CONCLUSION: Overall, US API women have the highest risk for GDM among all US racial/ethnic groups. However, APIs are a heterogeneous group by genetic background, culture, and diet and other lifestyle behaviors. Our findings imply that, whenever possible, API subgroups should be evaluated separately in health research. |
Occupational injuries among emergency responders
Reichard AA , Jackson LL . Am J Ind Med 2009 53 (1) 1-11 BACKGROUND: Emergency responders frequently incur injuries while providing medical, fire, and law enforcement services. National surveillance systems provide fragmented perspectives on responder injuries because they omit specific classes of workers (e.g., government or volunteers); they report only selected injuries; and employment information is incomplete. METHODS: We characterized injuries among emergency medical services (EMS), firefighting, and police occupations by using data from the National Electronic Injury Surveillance System-Occupational Supplement (NEISS-Work) for injuries treated in U.S. hospital emergency departments in 2000-2001. RESULTS: Sprains and strains were the leading injury (33-41%) among EMS, firefighter, and police occupations. Police officers and career firefighters had the highest injury rates (8.5 and 7.4 injuries per 100 full-time equivalent workers, respectively). CONCLUSIONS: The physical demands of emergency response are a leading cause of injuries that may benefit from similar interventions across the occupations. To assess risk, improved exposure data need to be acquired, particularly for volunteers. Am. J. Ind. Med. Published 2009 Wiley-Liss, Inc. |
Analytical performance criteria. Standardized surface dust sampling methods for metals, with emphasis on beryllium
Ashley K , Braybrooke G , Jahn SD , Brisson MJ , White KT . J Occup Environ Hyg 2009 6 (12) D97-100 Workers may become sensitized to beryllium via dermal contact with beryllium-containing dust.( Citation1 , Citation2 , Citation3 ) This exposure route, when coupled with subsequent inhalation exposures to airborne beryllium, has been hypothesized to lead to chronic beryllium disease (CBD).( Citation2 ) In efforts to monitor surface beryllium contamination and prevent dermal exposures due to contact with this highly toxic element, methods are needed for collection of surface dust for subsequent beryllium determination. | Surface contamination regulatory limits at U.S. Department of Energy (DOE) sites have been established by the Chronic Beryllium Disease Prevention Program Rule.( Citation4 ) These limits are 0.2 μg/100 cm2 for release of equipment from a beryllium area and 3 μg/100 cm2 as a housekeeping limit inside a beryllium area. Surface contamination limits are also under consideration by the U.S. Occupational Safety and Health Administration (OSHA) as part of a proposed rulemaking that is currently in progress.( Citation5 ) | Conformity in methods for sampling and analysis of beryllium from surfaces is desired, but inconsistencies in sampling and analytical practices often occur among industrial hygienists and laboratory personnel, respectively.( Citation6 ) If sampling and analysis methods are not standardized, analytical results from different investigators, locations, or points in time may not be comparable. Variations in sampling practices are of special concern, since the greatest contribution to measurement uncertainty in the overall analysis is ordinarily associated with sampling. Efforts to minimize measurement uncertainty through method standardization have been realized for many workplace toxicants and, as a consequence, standard methods for surface sampling of hazardous substances in workplaces have been promulgated. Standardized protocols for surface and dermal sampling have been produced by governmental agencies, e.g., OSHA and the U.S. National Institute for Occupational Safety and Health (NIOSH), as well as voluntary consensus standards bodies such as ASTM International. An ultimate goal is to provide standard surface sampling methods that will ensure comparability of data obtained from different locations and times. |
The effect of uncertainty in exposure estimation on the exposure-response relation between 1,3-butadiene and leukemia
Graff JJ , Sathiakumar N , Macaluso M , Maldonado G , Matthews R , Delzell E . Int J Environ Res Public Health 2009 6 (9) 2436-55 In a follow-up study of mortality among North American synthetic rubber industry workers, cumulative exposure to 1,3-butadiene was positively associated with leukemia. Problems with historical exposure estimation, however, may have distorted the association. To evaluate the impact of potential inaccuracies in exposure estimation, we conducted uncertainty analyses of the relation between cumulative exposure to butadiene and leukemia. We created the 1,000 sets of butadiene estimates using job-exposure matrices consisting of exposure values that corresponded to randomly selected percentiles of the approximate probability distribution of plant-, work area/job group-, and year specific butadiene ppm. We then analyzed the relation between cumulative exposure to butadiene and leukemia for each of the 1,000 sets of butadiene estimates. In the uncertainty analysis, the point estimate of the RR for the first non zero exposure category (>0-<37.5 ppm-years) was most likely to be about 1.5. The rate ratio for the second exposure category (37.5-<184.7 ppm-years) was most likely to range from 1.5 to 1.8. The RR for category 3 of exposure (184.7-<425.0 ppm-years) was most likely between 2.1 and 3.0. The RR for the highest exposure category (425.0+ ppm-years) was likely to be between 2.9 and 3.7. This range off RR point estimates can best be interpreted as a probability distribution that describes our uncertainty in RR point estimates due to uncertainty in exposure estimation. After considering the complete probability distributions of butadiene exposure estimates, the exposure-response association of butadiene and leukemia was maintained. This exercise was a unique example of how uncertainty analyses can be used to investigate and support an observed measure of effect when occupational exposure estimates are employed in the absence of direct exposure measurements. |
Physical activity advice to manage chronic conditions for adults with arthritis or hypertension, 2007
Carlson SA , Maynard LM , Fulton JE , Hootman JM , Yoon PW . Prev Med 2009 49 209-12 OBJECTIVE: To describe the prevalence and characteristics of persons with arthritis or hypertension who received advice from their health-care professional to manage their condition. METHODS: Data from 9 states were obtained from the 2007 Behavioral Risk Factor Surveillance System. Two modules (Arthritis Management and Actions to Control High Blood Pressure) were analyzed (sample sizes: arthritis 29,698, hypertension 29,783). RESULTS: Fifty-five percent of persons with arthritis and 75.8% of persons with hypertension reported that their health-care professional ever suggested physical activity or exercise to help manage their condition. Correlates for being less likely to receive advice were lower levels of education, longer time since last routine doctor visit, being physically inactive, and having lower body mass index. Among inactive, normal weight persons, 43.0% (95% CI: 38.7, 47.4) with arthritis and 50.0% (95% CI: 44.4, 55.6) with hypertension reported receiving advice; among inactive, obese patients, 59.1% (95% CI: 55.8, 62.3) with arthritis and 74.0% (95% CI: 70.5, 77.3) with hypertension reported receiving advice. CONCLUSIONS: Findings suggest that health-care professionals may base physical activity counseling more on body mass index than a patient's activity level. To manage chronic health conditions, health-care professionals should assess patient's physical activity and offer all patients appropriate counseling. |
The relative influence of different domains of social connectedness on self-directed violence in adolescence
Kaminski JW , Puddy RW , Hall DM , Cashman SY , Crosby AE , Ortega LA . J Youth Adolesc 2009 39 (5) 460-73 Previous research has linked greater social connectedness with a lowered risk of self-directed violence among adolescents. However, few studies have analyzed the comparative strength of different domains of connectedness (e.g., family, peers and school) to determine where limited resources might best be focused. Data to address that gap were taken from the Centers for Disease Control and Prevention's Student Health and Safety Survey, administered to 4,131 7th-12th graders (51.5% female; 43.8% Hispanic; 22.6% African American or Black). Logistic regressions (controlling for age, gender, race/ethnicity, family structure, academic performance, and depressive symptoms) suggest that family connectedness was a stronger predictor than connectedness to peers, school, or adults at school for non-suicidal self-harm, suicidal ideation, suicide plans, and non-fatal suicidal behavior. In some analyses, peer connectedness was unexpectedly a risk factor. Results have implications for prevention of suicide in adolescence, especially in the context of the current trend towards school-based prevention programs. |
Smoking prevalence among US veterans
Brown DW . J Gen Intern Med 2009 25 (2) 147-9 BACKGROUND/OBJECTIVE: Cigarette smoking is a significant health problem within the US military. Data from the 2003-2007 Behavioral Risk Factor Surveillance System (BRFSS) were used to estimate and compare the prevalence of smoking among US veterans with that of adults who did not serve in the US armed forces. METHODS: Data from the BRFSS, a state-based random-digit dialed telephone survey supported by the Centers for Disease Control and Prevention, were used to estimate the prevalence of current smoking among adults (aged ≥18 years) who reported ever serving on active duty in the United States Armed Forces. We compared, by birth cohort, age-adjusted smoking prevalence among veterans with that of adults who did not serve in the military. RESULTS: A total of 224,169 US veterans participated during 2003-2007. The age-adjusted prevalence of smoking during the period was 27.0% (standard error, 0.36) among veterans and 21% (0.12) among non-veterans. For both groups, the prevalence decreased across years from 29% (0.79) in 2003 to 25% (0.82) in 2007 among veterans and from 23% (0.29) in 2003 to 20% (0.26) in 2007 among non-veterans. Among veterans, smoking prevalence was highest among men born between 1975-1984 (36%; 90%CI = 33.7-37.5) and those born between 1985-1989 (37%; 90%CI = 31.7-48.2) with lower prevalences among men born between 1945-1954 (26%; 90%CI = 25.1-26.3), 1955-1964 (33%; 90%CI = 32.3-34.3), and 1965-1974 (27%; 90%CI = 26.0-28.1). The prevalence of smoking was 43% (90%CI = 39.0-47.6) among veterans with self-reported coronary heart disease (CHD), greater than that for non-veterans with CHD (31%; 90%CI = 28.6-33.1). CONCLUSIONS: Although the prevalence of smoking has declined among US adults, there are opportunities to further reduce smoking among US veterans, particularly young veterans for whom the prevalence of smoking is similar to that of the US adult population during the late 1960s/early 1970s. Continued work is necessary to target the high smoking prevalence among veterans with CHD, a group for which smoking cessation is especially important. |
Health-related behavior change after cancer: results of the American Cancer Society's studies of cancer survivors (SCS)
Hawkins NA , Smith T , Zhao L , Rodriguez J , Berkowitz Z , Stein KD . J Cancer Surviv 2009 4 (1) 20-32 INTRODUCTION: Cancer survivors are known to make positive health-related behavior changes after cancer, but less is known about negative behavior changes and correlates of behavior change. The present study was undertaken to examine positive and negative behavior changes after cancer and to identify medical, demographic, and psychosocial correlates of changes. METHODS: We analyzed data from a cross-sectional survey of 7,903 cancer survivors at 3, 6, and 11 years after diagnosis. RESULTS: Of 15 behaviors assessed, survivors reported 4 positive and 1 or 0 negative behavior changes. Positive change correlated with younger age, greater education, breast cancer, longer time since diagnosis, comorbidities, vitality, fear of recurrence, and spiritual well-being, while negative change correlated with younger age, being non-Hispanic African American, being widowed, divorced or separated, and lower physical and emotional health. Faith mediated the relationship between race/ethnicity and positive change. CONCLUSIONS: Cancer survivors were more likely to make positive than negative behavior changes after cancer. Demographic, medical, and psychosocial variables were associated with both types of changes. IMPLICATIONS FOR CANCER SURVIVORS: Results provide direction for behavior interventions and illustrate the importance of looking beyond medical and demographic variables to understand the motivators and barriers to positive behavior change after cancer. |
Tobacco use among Palestine refugee students (UNRWA) aged 13-15
Khader A , Shaheen Y , Turki Y , el Awa F , Fouad H , Warren CW , Jones NR , Lea V , Lee J . Prev Med 2009 49 224-8 OBJECTIVE: The United Nations Relief and Works Agency for Palestine Refugees in the Near East (UNRWA) has made tobacco use prevention a primary health issue. UNRWA provides education, health, relief and social services in five fields of operation: Jordan, Lebanon, Syria, Gaza Strip and the West Bank. The purpose of this paper is to compare tobacco use among Palestine refugee students and students in the general population of the five fields of operation. METHODS: Global Youth Tobacco Survey (GYTS) data were collected from representative samples of students in UNRWA schools in each of the five fields of operation in 2008. For comparison, previous data are included from GYTS conducted in Gaza Strip, Lebanon, and the West Bank (2005) and in Jordan and Syria (2007). Data are presented for three groups of students: refugees attending schools within and outside the camps and non-refugee students in the general population. RESULTS: In each of the five fields of operation, there was no difference in current cigarette smoking, current use of shisha, or susceptibility to initiate smoking among the three groups of students. Cigarette smoking and susceptibility was lowest in the Gaza Strip and highest in the West Bank; shisha use was lowest in the Gaza Strip but over 30% in Lebanon, Syria, and the West Bank. Exposure to secondhand smoke in public places was greater than 60% in almost all sites. Exposure to indirect advertising was almost 10%. CONCLUSIONS: The similarity in tobacco use among the three groups of students suggests that a coordinated plan between the UNRWA and the governmental authority could be most beneficial in reducing the burden of tobacco-related morbidity and mortality. |
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