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Concept: Influenza

895

Little is known about the amount and infectiousness of influenza virus shed into exhaled breath. This contributes to uncertainty about the importance of airborne influenza transmission. We screened 355 symptomatic volunteers with acute respiratory illness and report 142 cases with confirmed influenza infection who provided 218 paired nasopharyngeal (NP) and 30-minute breath samples (coarse >5-µm and fine ≤5-µm fractions) on days 1-3 after symptom onset. We assessed viral RNA copy number for all samples and cultured NP swabs and fine aerosols. We recovered infectious virus from 52 (39%) of the fine aerosols and 150 (89%) of the NP swabs with valid cultures. The geometric mean RNA copy numbers were 3.8 × 104/30-minutes fine-, 1.2 × 104/30-minutes coarse-aerosol sample, and 8.2 × 108 per NP swab. Fine- and coarse-aerosol viral RNA were positively associated with body mass index and number of coughs and negatively associated with increasing days since symptom onset in adjusted models. Fine-aerosol viral RNA was also positively associated with having influenza vaccination for both the current and prior season. NP swab viral RNA was positively associated with upper respiratory symptoms and negatively associated with age but was not significantly associated with fine- or coarse-aerosol viral RNA or their predictors. Sneezing was rare, and sneezing and coughing were not necessary for infectious aerosol generation. Our observations suggest that influenza infection in the upper and lower airways are compartmentalized and independent.

Concepts: Gene, Genetics, Infectious disease, Copy number variation, Virus, Influenza, Body mass index, Transmission and infection of H5N1

687

With over 3 billion airline passengers annually, the inflight transmission of infectious diseases is an important global health concern. Over a dozen cases of inflight transmission of serious infections have been documented, and air travel can serve as a conduit for the rapid spread of newly emerging infections and pandemics. Despite sensational media stories and anecdotes, the risks of transmission of respiratory viruses in an airplane cabin are unknown. Movements of passengers and crew may facilitate disease transmission. On 10 transcontinental US flights, we chronicled behaviors and movements of individuals in the economy cabin on single-aisle aircraft. We simulated transmission during flight based on these data. Our results indicate there is low probability of direct transmission to passengers not seated in close proximity to an infectious passenger. This data-driven, dynamic network transmission model of droplet-mediated respiratory disease is unique. To measure the true pathogen burden, our team collected 229 environmental samples during the flights. Although eight flights were during Influenza season, all qPCR assays for 18 common respiratory viruses were negative.

Concepts: Epidemiology, Disease, Infectious disease, Diseases and disorders, Infection, Influenza, Aircraft, Air travel

584

In the United States, annual vaccination against seasonal influenza is recommended for all persons aged ≥6 months (1). During each influenza season since 2004-05, CDC has estimated the effectiveness of seasonal influenza vaccine to prevent laboratory-confirmed influenza associated with medically attended acute respiratory illness (ARI). This report uses data from 4,562 children and adults enrolled in the U.S. Influenza Vaccine Effectiveness Network (U.S. Flu VE Network) during November 2, 2017-February 3, 2018. During this period, overall adjusted vaccine effectiveness (VE) against influenza A and influenza B virus infection associated with medically attended ARI was 36% (95% confidence interval [CI] = 27%-44%). Most (69%) influenza infections were caused by A(H3N2) viruses. VE was estimated to be 25% (CI = 13% to 36%) against illness caused by influenza A(H3N2) virus, 67% (CI = 54%-76%) against A(H1N1)pdm09 viruses, and 42% (CI = 25%-56%) against influenza B viruses. These early VE estimates underscore the need for ongoing influenza prevention and treatment measures. CDC continues to recommend influenza vaccination because the vaccine can still prevent some infections with currently circulating influenza viruses, which are expected to continue circulating for several weeks. Even with current vaccine effectiveness estimates, vaccination will still prevent influenza illness, including thousands of hospitalizations and deaths. Persons aged ≥6 months who have not yet been vaccinated this season should be vaccinated.

Concepts: Immune system, Infectious disease, Virus, Vaccine, Vaccination, Influenza, Influenza pandemic, Influenza vaccine

457

Ebola viruses (EBOV) cause often fatal hemorrhagic fever in several species of simian primates including human. While fruit bats are considered natural reservoir, involvement of other species in EBOV transmission is unclear. In 2009, Reston-EBOV was the first EBOV detected in swine with indicated transmission to humans. In-contact transmission of Zaire-EBOV (ZEBOV) between pigs was demonstrated experimentally. Here we show ZEBOV transmission from pigs to cynomolgus macaques without direct contact. Interestingly, transmission between macaques in similar housing conditions was never observed. Piglets inoculated oro-nasally with ZEBOV were transferred to the room housing macaques in an open inaccessible cage system. All macaques became infected. Infectious virus was detected in oro-nasal swabs of piglets, and in blood, swabs, and tissues of macaques. This is the first report of experimental interspecies virus transmission, with the macaques also used as a human surrogate. Our finding may influence prevention and control measures during EBOV outbreaks.

Concepts: Human, Influenza, Mammal, Primate, Ebola, Viral hemorrhagic fever, Simian, Crab-eating Macaque

365

Highly pathogenic avian H5N1 influenza A viruses occasionally infect humans, but currently do not transmit efficiently among humans. The viral haemagglutinin (HA) protein is a known host-range determinant as it mediates virus binding to host-specific cellular receptors. Here we assess the molecular changes in HA that would allow a virus possessing subtype H5 HA to be transmissible among mammals. We identified a reassortant H5 HA/H1N1 virus-comprising H5 HA (from an H5N1 virus) with four mutations and the remaining seven gene segments from a 2009 pandemic H1N1 virus-that was capable of droplet transmission in a ferret model. The transmissible H5 reassortant virus preferentially recognized human-type receptors, replicated efficiently in ferrets, caused lung lesions and weight loss, but was not highly pathogenic and did not cause mortality. These results indicate that H5 HA can convert to an HA that supports efficient viral transmission in mammals; however, we do not know whether the four mutations in the H5 HA identified here would render a wholly avian H5N1 virus transmissible. The genetic origin of the remaining seven viral gene segments may also critically contribute to transmissibility in mammals. Nevertheless, as H5N1 viruses continue to evolve and infect humans, receptor-binding variants of H5N1 viruses with pandemic potential, including avian-human reassortant viruses as tested here, may emerge. Our findings emphasize the need to prepare for potential pandemics caused by influenza viruses possessing H5 HA, and will help individuals conducting surveillance in regions with circulating H5N1 viruses to recognize key residues that predict the pandemic potential of isolates, which will inform the development, production and distribution of effective countermeasures.

Concepts: Virus, Influenza, Avian influenza, Influenza pandemic, Transmission and infection of H5N1, Pandemic, 2009 flu pandemic, Influenza A virus subtype H5N1

271

 The 2014-15 influenza season was distinguished by an A(H3N2) epidemic of antigenically-drifted virus and vaccine containing identical components to 2013-14. We report 2014-15 vaccine effectiveness (VE) estimates from Canada and explore contributing agent-host factors.

Concepts: Immune system, Infectious disease, Virus, Vaccine, Vaccination, Influenza, Avian influenza, Influenza vaccine

267

Background During the 2009 influenza A (H1N1) pandemic, pregnant women were at risk for severe influenza illness. This concern was complicated by questions about vaccine safety in pregnant women that were raised by anecdotal reports of fetal deaths after vaccination. Methods We explored the safety of influenza vaccination of pregnant women by linking Norwegian national registries and medical consultation data to determine influenza diagnosis, vaccination status, birth outcomes, and background information for pregnant women before, during, and after the pandemic. We used Cox regression models to estimate hazard ratios for fetal death, with the gestational day as the time metric and vaccination and pandemic exposure as time-dependent exposure variables. Results There were 117,347 eligible pregnancies in Norway from 2009 through 2010. Fetal mortality was 4.9 deaths per 1000 births. During the pandemic, 54% of pregnant women in their second or third trimester were vaccinated. Vaccination during pregnancy substantially reduced the risk of an influenza diagnosis (adjusted hazard ratio, 0.30; 95% confidence interval [CI], 0.25 to 0.34). Among pregnant women with a clinical diagnosis of influenza, the risk of fetal death was increased (adjusted hazard ratio, 1.91; 95% CI, 1.07 to 3.41). The risk of fetal death was reduced with vaccination during pregnancy, although this reduction was not significant (adjusted hazard ratio, 0.88; 95% CI, 0.66 to 1.17). Conclusions Pandemic influenza virus infection in pregnancy was associated with an increased risk of fetal death. Vaccination during pregnancy reduced the risk of an influenza diagnosis. Vaccination itself was not associated with increased fetal mortality and may have reduced the risk of influenza-related fetal death during the pandemic. (Funded by the Norwegian Institute of Public Health.).

Concepts: Pregnancy, Childbirth, Embryo, Fetus, Vaccination, Obstetrics, Influenza, Influenza vaccine

253

The avian H7N9 influenza outbreak in 2013 resulted from an unprecedented incidence of influenza transmission to humans from infected poultry. The majority of human H7N9 isolates contained a hemagglutinin (HA) mutation (Q226L) that has previously been associated with a switch in receptor specificity from avian-type (NeuAcα2-3Gal) to human-type (NeuAcα2-6Gal), as documented for the avian progenitors of the 1957 (H2N2) and 1968 (H3N2) human influenza pandemic viruses. While this raised concern that the H7N9 virus was adapting to humans, the mutation was not sufficient to switch the receptor specificity of H7N9, and has not resulted in sustained transmission in humans. To determine if the H7 HA was capable of acquiring human-type receptor specificity, we conducted mutation analyses. Remarkably, three amino acid mutations conferred a switch in specificity for human-type receptors that resembled the specificity of the 2009 human H1 pandemic virus, and promoted binding to human trachea epithelial cells.

Concepts: DNA, Protein, Influenza, Avian influenza, Influenza pandemic, Transmission and infection of H5N1, Pandemic, Human flu

240

H3N2 viruses continuously acquire mutations in the hemagglutinin (HA) glycoprotein that abrogate binding of human antibodies. During the 2014-2015 influenza season, clade 3C.2a H3N2 viruses possessing a new predicted glycosylation site in antigenic site B of HA emerged, and these viruses remain prevalent today. The 2016-2017 seasonal influenza vaccine was updated to include a clade 3C.2a H3N2 strain; however, the egg-adapted version of this viral strain lacks the new putative glycosylation site. Here, we biochemically demonstrate that the HA antigenic site B of circulating clade 3C.2a viruses is glycosylated. We show that antibodies elicited in ferrets and humans exposed to the egg-adapted 2016-2017 H3N2 vaccine strain poorly neutralize a glycosylated clade 3C.2a H3N2 virus. Importantly, antibodies elicited in ferrets infected with the current circulating H3N2 viral strain (that possesses the glycosylation site) and humans vaccinated with baculovirus-expressed H3 antigens (that possess the glycosylation site motif) were able to efficiently recognize a glycosylated clade 3C.2a H3N2 virus. We propose that differences in glycosylation between H3N2 egg-adapted vaccines and circulating strains likely contributed to reduced vaccine effectiveness during the 2016-2017 influenza season. Furthermore, our data suggest that influenza virus antigens prepared via systems not reliant on egg adaptations are more likely to elicit protective antibody responses that are not affected by glycosylation of antigenic site B of H3N2 HA.

Concepts: Immune system, Antibody, Microbiology, Virus, Vaccine, Vaccination, Influenza, Virology

237

A routine investigation by the New York City (NYC) Department of Health and Mental Hygiene (DOHMH) identified a nonpregnant woman in her twenties who reported she had engaged in a single event of condomless vaginal intercourse with a male partner the day she returned to NYC (day 0) from travel to an area with ongoing Zika virus transmission. She had headache and abdominal cramping while in the airport awaiting return to NYC. The following day (day 1) she developed fever, fatigue, a maculopapular rash, myalgia, arthralgia, back pain, swelling of the extremities, and numbness and tingling in her hands and feet. In addition, on day 1, the woman began menses that she described as heavier than usual. On day 3 she visited her primary care provider who obtained blood and urine specimens. Zika virus RNA was detected in both serum and urine by real-time reverse transcription-polymerase chain reaction (rRT-PCR) performed at the DOHMH Public Health Laboratory using a test based on an assay developed at CDC (1). The results of serum testing for anti-Zika virus immunoglobulin M (IgM) antibody performed by the New York State Department of Health Wadsworth Center laboratory was negative using the CDC Zika IgM antibody capture enzyme-linked immunosorbent assay (Zika MAC-ELISA) (2).

Concepts: Immune system, Antibody, Immunology, Influenza, ELISA, ELISPOT, New York City, New York