Margaret Carrel

Evolution of highly pathogenic H5N1 avian influenza viruses in Vietnam between 2001 and 2007

Highly pathogenic avian influenza (HPAI) H5N1 viruses have caused dramatic economic losses to the poultry industry of Vietnam and continue to pose a serious threat to public health. As of June 2008, Vietnam had reported nearly one third of worldwide laboratory confirmed human H5N1 infections. To better understand the emergence, spread and evolution of H5N1 in Vietnam we studied over 300 H5N1 avian influenza viruses isolated from Vietnam since their first detection in 2001. Our phylogenetic analyses indicated that six genetically distinct H5N1 viruses were introduced into Vietnam during the past seven years. The H5N1 lineage that evolved following the introduction in 2003 of the A/duck/Hong Kong/821/2002-like viruses, with clade 1 hemagglutinin (HA), continued to predominate in southern Vietnam as of May 2007. A virus with a clade 2.3.4 HA newly introduced into northern Vietnam in 2007, reassorted with pre-existing clade 1 viruses, resulting in the emergence of novel genotypes with neuraminidase (NA) and/or internal gene segments from clade 1 viruses. A total of nine distinct genotypes have been present in Vietnam since 2001, including five that were circulating in 2007. At least four of these genotypes appear to have originated in Vietnam and represent novel H5N1 viruses not reported elsewhere. Geographic and temporal analyses of H5N1 infection dynamics in poultry suggest that the majority of viruses containing new genes were first detected in northern Vietnam and subsequently spread to southern Vietnam after reassorting with pre-existing local viruses in northern Vietnam. Although the routes of entry and spread of H5N1 in Vietnam remain speculative, enhanced poultry import controls and virologic surveillance efforts may help curb the entry and spread of new HPAI viral genes.

Regional Variation in Out-of-Hospital Cardiac Arrest Survival in the United States

Background— Although previous studies have shown marked variation in out-of-hospital cardiac arrest survival across US regions, factors underlying this survival variation remain incompletely explained. Methods and Results— Using data from the Cardiac Arrest Registry to Enhance Survival, we identified 96 662 adult patients with out-of-hospital cardiac arrest in 132 US counties. We used hierarchical regression models to examine county-level variation in rates of survival and survival with functional recovery (defined as Cerebral Performance Category score of 1 or 2) and examined the contribution of demographics, cardiac arrest characteristics, bystander cardiopulmonary resuscitation, automated external defibrillator use, and county-level sociodemographic factors in survival variation across counties. A total of 9317 (9.6%) patients survived to discharge, and 7176 (7.4%) achieved functional recovery. At a county level, there was marked variation in rates of survival to discharge (range, 3.4%–22.0%; median odds ratio, 1.40; 95% confidence interval, 1.32–1.46) and survival with functional recovery (range, 0.8%–21.0%; median odds ratio, 1.53; 95% confidence interval, 1.43–1.62). County-level rates of bystander cardiopulmonary resuscitation and automated external defibrillator use were positively correlated with both outcomes (P<0.0001 for all). Patient demographic and cardiac arrest characteristics explained 4.8% and 27.7% of the county-level variation in survival, respectively. Additional adjustment of bystander cardiopulmonary resuscitation and automated external defibrillator explained 41% of the survival variation, and this increased to 50.4% after adjustment of county-level sociodemographic factors. Similar findings were noted in analyses of survival with functional recovery. Conclusions— Although out-of-hospital cardiac arrest survival varies significantly across US counties, a substantial proportion of the variation is attributable to differences in bystander response across communities.

USA300 Methicillin-Resistant Staphylococcus aureus, United States, 2000-2013.

We confirm USA300 in the West and Midwest and subsequent diffusion to the East Coast.

Trends in Prevalent and Incident Opioid Receipt: an Observational Study in Veterans Health Administration 2004–2012

ABSTRACTBackgroundImproved understanding of temporal and regional trends may support safe and effective prescribing of opioids.ObjectiveWe describe national, regional, and facility-level trends and variations in opioid receipt between fiscal years (FY) 2004 and 2012.DesignObservational cohort study using Veterans Health Administration (VHA) administrative databases.ParticipantsAll patients receiving primary care within 137 VHA healthcare systems during a given study year and receiving medications from VHA one year before and during a given study year.Main MeasuresPrevalent and incident opioid receipt during each year of the study period.Key ResultsThe overall prevalence of opioid receipt increased from 18.9 % of all veteran outpatients in FY2004 to 33.4 % in FY2012, a 76.7 % relative increase. In FY2012, women had higher rates of prevalent opioid receipt than men (42.4 % vs. 32.9 %), and the youngest veterans (18–34 years) had higher prevalent opioid receipt compared to the oldest veterans (≥80 years) (47.6 % vs. 17.9 %). All regions in the United States saw increased rates of prevalent opioid receipt during this time period. Prevalence rates varied widely by facility: in FY2012, the lowest-prescribing facility had a rate of 13.5 %, and the highest of 50.8 %. Annual incident opioid receipt increased from 8.8 % in FY2004 to 10.2 % in FY2011, with a decline to 9.8 % in FY2012. Incident prescribing increased at some facilities and decreased at others. Facilities with high prevalent prescribing tended to have flat or decreasing incident prescribing rates during the study time frame.ConclusionsRates of opioid receipt increased throughout the study time frame, with wide variation in prevalent and incident rates across geographical region, sex, and age groups. Prevalence and incidence rates reflect distinct prescribing practices. Areas with the highest prevalence tended to have lower increases in incident opioid receipt over the study period. This likely reflects facility-level variations in prescribing practices as well as baseline rates of prevalent use. Future work assessing opioid prescribing should employ methodologies to account for and interpret both prevalent and incident opioid receipt.

Swine Farming Is a Risk Factor for Infection With and High Prevalence of Carriage of Multidrug-Resistant Staphylococcus aureus

BACKGROUND Livestock-associated Staphylococcus aureus (LA-SA) has been documented worldwide. However, much remains unknown about LA-SA colonization and infection, especially in rural environments. METHODS We conducted a large-scale prospective study of 1342 Iowans, including individuals with livestock contact and a community-based comparison group. Nasal and throat swabs were collected to determine colonization at enrollment, and skin infection swabs over 17 months were assessed for S. aureus. Outcomes included carriage of S. aureus, methicillin-resistant S. aureus (MRSA), tetracycline-resistant S. aureus (TRSA), multidrug-resistant S. aureus (MDRSA), and LA-SA. RESULTS Of 1342 participants, 351 (26.2%; 95% confidence interval [CI], 23.8%-28.6%) carried S. aureus. MRSA was isolated from 34 (2.5%; 95% CI, 1.8%-3.5%) and LA-SA from 131 (9.8%; 95% CI, 8.3%-11.5%) of the 1342 participants. Individuals with current swine exposure were significantly more likely to carry S. aureus (prevalence ratio [PR], 1.8; 95% CI, 1.4-2.2), TRSA (PR, 8.4; 95% CI, 5.6-12.6), MDRSA (PR, 6.1; 95% CI, 3.8-10.0), and LA-SA (PR, 5.8; 95% CI, 3.9-8.4) than those lacking exposure. Skin infections (n = 103) were reported from 67 individuals, yielding an incidence rate of 6.6 (95% CI, 4.9-8.9) per 1000 person-months. CONCLUSIONS Current swine workers are 6 times more likely to carry MDRSA than those without current swine exposure. We observed active infections caused by LA-SA. This finding suggests that individuals with livestock contact may have a high prevalence of exposure to, and potentially infection with, antibiotic-resistant S. aureus strains, including LA-SA strains.

Demographic and health surveillance: longitudinal ethical considerations

Longitudinal data gathered from health surveillance, when combined with detailed demographic information, can provide invaluable insight into disease outcomes. Many such surveillance sites exist in the developing world, particularly in Asia and sub-Saharan Africa, and focus on diseases such as HIV/AIDS, cholera, malaria and tuberculosis. The indistinct positions of such surveillance systems, often inhabiting an area between research, treatment and population health monitoring, means that the necessity of and responsibility for ethical oversight is unclear. This regulatory vacuum is further compounded by a lack of attention to longitudinal surveillance systems in ethics literature. In this paper, we explore some key ethical questions that arise during demographic and health surveillance in relation to ethical principles of beneficence, respect for persons and justice: health-care provision, informed consent and study sustainability.

Residential Proximity to Large Numbers of Swine in Feeding Operations Is Associated with Increased Risk of Methicillin-Resistant Staphylococcus aureus Colonization at Time of Hospital Admission in Rural Iowa Veterans

Among 1,036 patients, residential proximity within 1 mile of large swine facilities was associated with nearly double the risk of methicillin-resistant Staphylococcus aureus (MRSA) colonization at admission (relative risk, 1.8786 [95% confidence interval, 1.0928-3.2289]; P = .0239) and, after controlling for multiple admissions and age, was associated with nearly triple the odds of MRSA colonization (odds ratio, 2.76 [95% confidence interval, 1.2728-5.9875]; P = .0101).

Spatiotemporal structure of molecular evolution of H5N1 highly pathogenic avian influenza viruses in Vietnam.

Background Vietnam is one of the countries most affected by outbreaks of H5N1 highly pathogenic avian influenza viruses. First identified in Vietnam in poultry in 2001 and in humans in 2004, the virus has since caused 111 cases and 56 deaths in humans. In 2003/2004 H5N1 outbreaks, nearly the entire poultry population of Vietnam was culled. Our earlier study (Wan et al., 2008, PLoS ONE, 3(10): e3462) demonstrated that there have been at least six independent H5N1 introductions into Vietnam and there were nine newly emerged reassortants from 2001 to 2007 in Vietnam. H5N1 viruses in Vietnam cluster distinctly around Hanoi and Ho Chi Minh City. However, the nature of the relationship between genetic divergence and geographic patterns is still unclear. Methodology/Principal Findings In this study, we hypothesized that genetic distances between H5N1 viruses in Vietnam are correlated with geographic distances, as the result of distinct population and environment patterns along Vietnams long north to south longitudinal extent. Based on this hypothesis, we combined spatial statistical methods with genetic analytic techniques and explicitly used geographic space to explore genetic evolution of H5N1 highly pathogenic avian influenza viruses at the sub-national scale in Vietnam. Our dataset consisted of 125 influenza viruses (with whole genome sets) isolated in Vietnam from 2003 to 2007. Our results document the significant effect of space and time on genetic evolution and the rise of two regional centers of genetic mixing by 2007. These findings give insight into processes underlying viral evolution and suggest that genetic differentiation is associated with the distance between concentrations of human and poultry populations around Hanoi and Ho Chi Minh City. Conclusions/Significance The results show that genetic evolution of H5N1 viruses in Vietnamese domestic poultry is highly correlated with the location and spread of those viruses in geographic space. This correlation varies by scale, time, and gene, though a classic isolation by distance pattern is observed. This study is the first to characterize the geographic structure of influenza viral evolution at the sub-national scale in Vietnam and can shed light on how H5N1 HPAIVs evolve in certain geographic settings.

Spatio-temporal clustering of cholera: The impact of flood control in Matlab, Bangladesh, 1983–2003

Introducing flood control to an area of endemic waterborne diseases could have significant impacts on spatio-temporal occurrence of cholera. Using 21-year data from Bangladesh, we conducted cluster analysis to explore changes in spatial and temporal distribution of cholera incidence since the construction of flood control structures. Striking changes in temporal cluster patterns emerged, including a shift from dry-season to rainy-season clusters following flood protection and delayed clustering inside the protected areas. Spatial differences in pre-flood protection and post-protection cholera clusters are weaker. Changes in spatio-temporal cholera clustering, associated with implementation of flood protection strategies, could affect local cholera prevention efforts.

Personal Belief Exemptions to Vaccination in California: A Spatial Analysis

BACKGROUND: School vaccination rates in California have fallen as more parents opt for personal belief exemptions (PBEs) for their children. Our goals were to (1) spatially analyze PBE patterns over time, (2) determine correlates of PBEs, and (3) examine their spatial overlap with personal medical exemptions (PMEs). METHODS: PBE and PME data for California kindergarten classes from the 2001/2002 to 2013/2014 school years were matched to the locations of schools. Nonspatial clustering algorithms were implemented to group 5147 schools according to their trends in PBE percentages among kindergartners. Cluster assignments were mapped and hotspot analysis was performed to find areas in California where schools sharing trends in PBEs over time were colocated. Schools were further associated both with school-level data on minority enrollment and free and reduced price lunch participation and with charter/private and rural/urban status. Spatial regression was implemented to determine which school-level variables were correlated with PBE rates in the 2013/2014 school year. RESULTS: Distinct spatial patterns are observed in California when PBE cluster assignments are mapped. Results indicate that schools belonging to the “high PBE” cluster are spatially buffered from those in “low PBE” areas by “medium PBE” schools. Further, PBE rates are positively associated with the percentage of white students, charter status, and private schools. CONCLUSIONS: Hotspots of high PBE schools are in some cases colocated with schools that have elevated PME rates, prompting concern that herd immunity is diminished for school populations where students have no choice but to remain unvaccinated.