Antiviral Susceptibility of Highly Pathogenic Avian Influenza A(H5N1) Viruses Isolated from Poultry,Vietnam, 2009–2011

We assessed drug susceptibilities of 125 avian influenza A(H5N1) viruses isolated from poultry in Vietnam during 2009–2011. Of 25 clade 1.1 viruses, all possessed a marker of resistance to M2 blockers amantadine and rimantadine; 24 were inhibited by neuraminidase inhibitors. One clade 1.1 virus contained the R430W neuraminidase gene and reduced inhibition by oseltamivir, zanamivir, and laninamivir 12-, 73-, and 29-fold, respectively. Three of 30 clade 2.3.4 viruses contained a I223T mutation and showed 7-fold reduced inhibition by oseltamivir. One of 70 clade 2.3.2.1 viruses had the H275Y marker of oseltamivir resistance and exhibited highly reduced inhibition by oseltamivir and peramivir; antiviral agents DAS181 and favipiravir inhibited H275Y mutant virus replication in MDCK-SIAT1 cells. Replicative fitness of the H275Y mutant virus was comparable to that of wildtype virus. These findings highlight the role of drug susceptibility monitoring of H5N1 subtype viruses circulating among birds to inform antiviral stockpiling decisions for pandemic preparedness.     

Influenza A Subtype H3 Viruses in Feral Swine,United States, 2011–2012

To determine whether, and to what extent, influenza A subtype H3 viruses were present in feral swine in the United States, we conducted serologic and virologic surveillance during October 2011–September 2012. These animals were periodically exposed to and infected with A(H3N2) viruses, suggesting they may threaten human and animal health.     

Highly Pathogenic Avian Influenza Viruses and Generation of Novel Reassortants,United States, 2014–2015

Asian highly pathogenic avian influenza A(H5N8) viruses spread into North America in 2014 during autumn bird migration. Complete genome sequencing and phylogenetic analysis of 32 H5 viruses identified novel H5N1, H5N2, and H5N8 viruses that emerged in late 2014 through reassortment with North American low-pathogenicity avian influenza viruses.     

Human and animal rabies prevention and control cost in Bhutan, 2001–2008: The cost–benefit of dog rabies elimination

The objective of this study was to estimate the cost of various interventions and to quantify the economic impacts of rabies in Bhutan. Cost–benefit of dog rabies elimination versus human post exposure treatment cost was also assessed. The average direct medical cost of human post-exposure treatment (using rabies vaccine only) was estimated to be Nu. 1615 (US$ 35.65) per 5-dose Essen regimen per patient. The cost would increase to Nu. 2497 (US$ 55.13) and Nu. 19,633 (US$ 433.41) per patient when one dose of either equine rabies immunoglobulin (ERIG) or human rabies immunoglobulin (HRIG) is administered, respectively. The societal cost (direct medical and indirect patient expenses) per patient was estimated to be Nu. 2019 (US$ 45), Nu. 2901 (US$ 64) and Nu. 20,037 (US$ 442) using vaccine only, vaccine with ERIG and vaccine with HRIG, respectively. The average cost per dog vaccination and sterilization were estimated to be Nu. 75 (US$ 1.66) and Nu. 288 (US$ 6.36), respectively. The total direct cost of rabies and various interventions between 2001 and 2008 was estimated to be Nu. 46.95 million (US$ 1.03 million). The direct cost for intensified human PET was estimated to be Nu. 5.85 million (US$ 0.11 million) per year with a cumulated estimated costs of Nu. 35.10 million (US$ 0.70 million) while the cost of mass dog vaccination with at least 70% coverage is estimated to be approximately Nu. 10.31 million (US$ 0.21 million) at the end of 6 years. The combined cost of mass dog vaccination and human PET was estimated to be greater than the cost of human PET alone during the first 2 years of the campaign, and then would be lower than human PET cost alone after the 5th year of the campaign. The total cumulated cost of the combined strategy was estimated to be Nu. 34.14 million (US$ 0.73 million) and would be lower than the cumulated cost of human PET alone (Nu. 35.10 million, US$ 0.77 million) at the end of 6 years. Rabies represents a substantial economic impact to the Bhutanese society. Well-planned and implemented mass dog vaccination would result in elimination of rabies reservoirs in the domestic dog population and would eliminate human rabies cases. It would also reduce the recurrent expenditure on human post-exposure treatment.     

Oseltamivir-Resistant Influenza A(H1N1)pdm09 Viruses,United States, 2013–14

We report characteristics of oseltamivir-resistant influenza A(H1N1)pdm09 viruses and patients infected with these viruses in the United States. During 2013–14, fifty-nine (1.2%) of 4,968 analyzed US influenza A(H1N1)pdm09 viruses had the H275Y oseltamivir resistance–conferring neuraminidase substitution. Our results emphasize the need for local surveillance for neuraminidase inhibitor susceptibility among circulating influenza viruses.     

Increased Number of Human Cases of Influenza Virus A(H5N1) Infection,Egypt, 2014–15

During November 2014–April 2015, a total of 165 case-patients with influenza virus A(H5N1) infection, including 6 clusters and 51 deaths, were identified in Egypt. Among infected persons, 99% reported poultry exposure: 19% to ill poultry and 35% to dead poultry. Only 1 person reported wearing personal protective equipment while working with poultry.     

Pandemic Influenza Planning,United States, 1978–2008

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

Timing of Influenza A(H5N1) in Poultry and Humans and Seasonal Influenza Activity Worldwide, 2004–2013

Co-circulation of influenza A(H5N1) and seasonal influenza viruses among humans and animals could lead to co-infections, reassortment, and emergence of novel viruses with pandemic potential. We assessed the timing of subtype H5N1 outbreaks among poultry, human H5N1 cases, and human seasonal influenza in 8 countries that reported 97% of all human H5N1 cases and 90% of all poultry H5N1 outbreaks. In these countries, most outbreaks among poultry (7,001/11,331, 62%) and half of human cases (313/625, 50%) occurred during January–March. Human H5N1 cases occurred in 167 (45%) of 372 months during which outbreaks among poultry occurred, compared with 59 (10%) of 574 months that had no outbreaks among poultry. Human H5N1 cases also occurred in 59 (22%) of 267 months during seasonal influenza periods. To reduce risk for co-infection, surveillance and control of H5N1 should be enhanced during January–March, when H5N1 outbreaks typically occur and overlap with seasonal influenza virus circulation.     

Timeliness of Pediatric Influenza Vaccination Compared With Seasonal Influenza Activity in an Urban Community, 2004–2008

Objectives. We assessed pediatric influenza vaccination in relation to community influenza activity.Methods. We examined seasonal influenza vaccination in 34 012 children aged 6 months through 18 years from 5 academically affiliated clinics in northern Manhattan, New York (an urban low-income community) during the 2004–2008 seasons using hospital and city immunization registries. We calculated the cumulative number of administered influenza vaccine doses and proportion of children with any (≥ 1 dose) or full (1–2 doses per age recommendations) vaccination at the onset and peak of community polymerase chain reaction–confirmed influenza activity according to state surveillance reports and by March 31 each season.Results. Influenza vaccine administration began before October 1, peaked before influenza activity onset, and declined gradually over each season. Coverage at influenza activity onset, peak, and by March 31 increased over the 5 seasons. However, most children lacked full vaccination at these time points, particularly adolescents, minorities, and those requiring 2 doses.Conclusions. Despite early initiation of influenza vaccination, few children were fully vaccinated when influenza began circulating. Interventions should address factors negatively affecting timely influenza vaccination, especially in high-risk populations.Influenza epidemics typically occur from late fall to early spring and are associated with considerable morbidity and mortality, particularly among high-risk populations such as children younger than 5 years and individuals with chronic medical conditions.1 Influenza vaccination of children is an effective strategy for preventing infection and associated complications at the individual and community levels.2–6 The timing of vaccination may be particularly important for optimizing this protection. Influenza virus strains frequently change between seasons, and influenza vaccine efficacy wanes over time; thus, annual influenza vaccination is necessary.7–9 Moreover, influenza viruses begin to circulate in communities at varying times each year, and immunity against influenza may take time to be achieved following vaccine administration.10–13 Therefore, the Advisory Committee on Immunization Practices recommends influenza vaccination of all individuals aged 6 months and older as soon as vaccine becomes available each season, ideally before the community onset of influenza activity.9Despite this recommendation, seasonal influenza vaccination coverage of children by March 31 is low, and limited data suggest that many of those who are vaccinated do not receive it early in the season.14–20 A previous study found that many adults failed to receive influenza vaccine before the peak of influenza activity despite seeing their physician during the early vaccination period.21 To our knowledge, the timing of pediatric influenza vaccination directly compared with community influenza activity in a given season has not yet been examined. Such investigation is particularly warranted among urban low-income minority children, who are at increased risk for inadequate influenza vaccination, viral transmission, and influenza-associated morbidity and mortality.15,17,22,23We assessed influenza vaccination of predominantly low-income minority children at the onset and peak of influenza activity in an urban community and by March 31 during 5 influenza seasons. We also identified determinants of timely vaccination in this population.     

Bisphenol A and Reproductive Health: Update of Experimental and Human Evidence, 2007–2013

Background: In 2007, an expert panel reviewed associations between bisphenol A (BPA) exposure and reproductive health outcomes. Since then, new studies have been conducted on the impact of BPA on reproduction.Objective: In this review, we summarize data obtained since 2007, focusing on a) findings from human and animal studies, b) the effects of BPA on a variety of reproductive end points, and c) mechanisms of BPA action.Methods: We reviewed the literature published from 2007 to 2013 using a PubMed search based on keywords related to BPA and male and female reproduction.Discussion: Because BPA has been reported to affect the onset of meiosis in both animal and in vitro models, interfere with germ cell nest breakdown in animal models, accelerate follicle transition in several animal species, alter steroidogenesis in multiple animal models and women, and reduce oocyte quality in animal models and women undergoing in vitro fertilization (IVF), we consider it an ovarian toxicant. In addition, strong evidence suggests that BPA is a uterine toxicant because it impaired uterine endometrial proliferation, decreased uterine receptivity, and increased implantation failure in animal models. BPA exposure may be associated with adverse birth outcomes, hyperandrogenism, sexual dysfunction, and impaired implantation in humans, but additional studies are required to confirm these associations. Studies also suggest that BPA may be a testicular toxicant in animal models, but the data in humans are equivocal. Finally, insufficient evidence exists regarding effects of BPA on the oviduct, the placenta, and pubertal development.Conclusion: Based on reports that BPA impacts female reproduction and has the potential to affect male reproductive systems in humans and animals, we conclude that BPA is a reproductive toxicant.Citation: Peretz J, Vrooman L, Ricke WA, Hunt PA, Ehrlich S, Hauser R, Padmanabhan V, Taylor HS, Swan SH, VandeVoort CA, Flaws JA. 2014. Bisphenol A and reproductive health: update of experimental and human evidence, 2007–2013. Environ Health Perspect 122:775–786; http://dx.doi.org/10.1289/ehp.1307728     

Oseltamivir-Resistant Influenza Viruses A (H1N1) during 2007�C2009 Influenza Seasons, Japan

To monitor oseltamivir-resistant influenza viruses A (H1N1) (ORVs) with H275Y in neuraminidase (NA) in Japan during 2 influenza seasons, we analyzed 3,216 clinical samples by NA sequencing and/or NA inhibition assay. The total frequency of ORVs was 2.6% (45/1,734) during the 2007–08 season and 99.7% (1,477/1,482) during the 2008–09 season, indicating a marked increase in ORVs in Japan during 1 influenza season. The NA gene of ORVs in the 2007–08 season fell into 2 distinct lineages by D354G substitution, whereas that of ORVs in the 2008–09 season fell into 1 lineage. NA inhibition assay and M2 sequencing showed that almost all the ORVs were sensitive to zanamivir and amantadine. The hemagglutination inhibition test showed that ORVs were antigenetically similar to the 2008–09 vaccine strain A/Brisbane/59/2007. Our data indicate that the current vaccine or zanamivir and amantadine are effective against recent ORVs, but continuous surveillance remains necessary.     

Poultry Market Closures and Human Infection with Influenza A(H7N9) Virus,China, 2013–14

Closure of live poultry markets was implemented in areas affected by the influenza virus A(H7N9) outbreak in China during winter, 2013–14. Our analysis showed that closing live poultry markets in the most affected cities of Guangdong and Zhejiang provinces was highly effective in reducing the risk for H7N9 infection in humans.     

Severity of Influenza A(H1N1) Illness and Emergence of D225G Variant, 2013–14 Influenza Season,Florida, USA

Despite a regional decline in influenza A(H1N1)pdm09 virus infections during 2013–14, cases at a Florida hospital were more severe than those during 2009–10. Examined strains had a hemagglutinin polymorphism associated with enhanced binding to lower respiratory tract receptors. Genetic changes in this virus must be monitored to predict the effect of future pandemic viruses.     

Deaths Associated with Respiratory Syncytial and Influenza Viruses among Persons ≥5 Years of Age in HIV-Prevalent Area,South Africa, 1998–20091

We estimated deaths attributable to influenza and respiratory syncytial virus (RSV) among persons >5 years of age in South Africa during 1998–2009 by applying regression models to monthly deaths and laboratory surveillance data. Rates were expressed per 100,000 person-years. The mean annual number of seasonal influenza–associated deaths was 9,093 (rate 21.6). Persons >65 years of age and HIV-positive persons accounted for 50% (n = 4,552) and 28% (n = 2,564) of overall seasonal influenza-associated deaths, respectively. In 2009, we estimated 4,113 (rate 9.2) influenza A(H1N1)pdm09–associated deaths. The mean of annual RSV-associated deaths during the study period was 511 (rate 1.2); no RSV-associated deaths were estimated in persons >45 years of age. Our findings support the recommendation for influenza vaccination of older persons and HIV-positive persons. Surveillance for RSV should be strengthened to clarify the public health implications and severity of illness associated with RSV infection in South Africa.     

Epidemiology of Influenza A Virus among Black-headed Gulls,the Netherlands, 2006–2010

We sampled 7,511 black-headed gulls for influenza virus in the Netherlands during 2006–2010 and found that subtypes H13 and H16 caused annual epidemics in fledglings on colony sites. Our findings validate targeted surveillance of wild waterbirds and clarify underlying factors for influenza virus emergence in other species.