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Concept: Pandemic


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


The 14th-18th century pandemic of Yersinia pestis caused devastating disease outbreaks in Europe for almost 400 years. The reasons for plague’s persistence and abrupt disappearance in Europe are poorly understood, but could have been due to either the presence of now-extinct plague foci in Europe itself, or successive disease introductions from other locations. Here we present five Y. pestis genomes from one of the last European outbreaks of plague, from 1722 in Marseille, France. The lineage identified has not been found in any extant Y. pestis foci sampled to date, and has its ancestry in strains obtained from victims of the 14th century Black Death. These data suggest the existence of a previously uncharacterized historical plague focus that persisted for at least three centuries. We propose that this disease source may have been responsible for the many resurgences of plague in Europe following the Black Death.

Concepts: Pandemic, Italy, Yersinia pestis, Bubonic plague, Black Death, Plague, Third Pandemic, London


The Black Death, originating in Asia, arrived in the Mediterranean harbors of Europe in 1347 CE, via the land and sea trade routes of the ancient Silk Road system. This epidemic marked the start of the second plague pandemic, which lasted in Europe until the early 19th century. This pandemic is generally understood as the consequence of a singular introduction of Yersinia pestis, after which the disease established itself in European rodents over four centuries. To locate these putative plague reservoirs, we studied the climate fluctuations that preceded regional plague epidemics, based on a dataset of 7,711 georeferenced historical plague outbreaks and 15 annually resolved tree-ring records from Europe and Asia. We provide evidence for repeated climate-driven reintroductions of the bacterium into European harbors from reservoirs in Asia, with a delay of 15 ± 1 y. Our analysis finds no support for the existence of permanent plague reservoirs in medieval Europe.

Concepts: Infectious disease, Middle Ages, Europe, Pandemic, Italy, Yersinia pestis, Black Death, Silk Road


Concerns have been raised over competing interests (CoI) among academics during the 2009 to 2010 A/H1N1 pandemic. Media reporting can influence public anxiety and demand for pharmaceutical products. We assessed CoI of academics providing media commentary during the early stages of the pandemic.

Concepts: Influenza, Swine influenza, Pandemic, Influenza vaccine, 2009 flu pandemic, Influenza A virus subtype H1N1, Pandemic H1N1/09 virus, H1N1


The spatiotemporal evolution of human mobility and the related fluctuations of population density are known to be key drivers of the dynamics of infectious disease outbreaks. These factors are particularly relevant in the case of mass gatherings, which may act as hotspots of disease transmission and spread. Understanding these dynamics, however, is usually limited by the lack of accurate data, especially in developing countries. Mobile phone call data provide a new, first-order source of information that allows the tracking of the evolution of mobility fluxes with high resolution in space and time. Here, we analyze a dataset of mobile phone records of ∼150,000 users in Senegal to extract human mobility fluxes and directly incorporate them into a spatially explicit, dynamic epidemiological framework. Our model, which also takes into account other drivers of disease transmission such as rainfall, is applied to the 2005 cholera outbreak in Senegal, which totaled more than 30,000 reported cases. Our findings highlight the major influence that a mass gathering, which took place during the initial phase of the outbreak, had on the course of the epidemic. Such an effect could not be explained by classic, static approaches describing human mobility. Model results also show how concentrated efforts toward disease control in a transmission hotspot could have an important effect on the large-scale progression of an outbreak.

Concepts: Epidemiology, Disease, Infectious disease, Infectious diseases, Pandemic, Mobile phone, Cholera, Outbreak


To the Editor: Avian-origin influenza A (H7N9) viruses emerged as human pathogens in China in 2013 and have caused 137 cases and 45 deaths to date.(1) These viruses have acquired mutations that could facilitate infection in mammals,(2) which could pose a pandemic threat if the viruses become readily transmissible in humans. Vaccines are a key defense against pandemics, but candidate vaccines featuring H7 hemagglutinins (HA) have been poorly immunogenic.(3) We have previously described the development, manufacture, and efficacy in mice of an A/Anhui/1/13 (H7N9) viruslike particle (VLP) vaccine produced in insect cells with the use of recombinant baculovirus. This vaccine . . .

Concepts: Immune system, Microbiology, Vaccine, Vaccination, Influenza, Influenza pandemic, Pandemic, Influenza vaccine


Influenza A H5N1 has killed millions of birds and raises serious public health concern because of its potential to spread to humans and cause a global pandemic. While the early focus was in Asia, recent evidence suggests that Egypt is a new epicenter for the disease. This includes characterization of a variant clade, which has been found almost exclusively in Egypt.We analyzed 226 HA and 92 NA sequences with an emphasis on the H5N1 strains in Egypt using a Bayesian discrete phylogeography approach. This allowed modeling of virus dispersion between Egyptian governorates including the most likely origin.

Concepts: Public health, Epidemiology, Influenza, Avian influenza, Influenza pandemic, Pandemic, 2009 flu pandemic, Egypt


Perhaps the only good news from the tragic Ebola epidemic in Guinea, Sierra Leone, and Liberia is that it may serve as a wake-up call: we must prepare for future epidemics of diseases that may spread more effectively than Ebola. There is a significant chance that an epidemic of a substantially more infectious disease will occur sometime in the next 20 years; after all, we saw major epidemics during the 20th century, including the Spanish influenza epidemic of 1918-1919 and the ongoing pandemic of human immunodeficiency virus. In fact, of all the things that could kill more than 10 million . . .

Concepts: Epidemiology, Infectious disease, Infection, Influenza, Pandemic, Liberia, Sierra Leone, Guinea


Mark Siedner and colleagues reflect on the early response to the Ebola epidemic and lessons that can be learned for future epidemics.

Concepts: Epidemiology, African American, Pandemic, Native Americans in the United States, Epidemic, Midwestern United States, Western United States


The 2010 Haitian earthquake and consequent Cholera epidemic taxed the already fragile health system. A large number of humanitarian organizations participated in the disaster response and the health communication response was analysed. Health Cluster updates from both periods were analysed for contents with a World Health Organization draft check list for monitoring and evaluating the quality of epidemiological data contained in WHO and Health Cluster emergency reports. The Pan-American Health Organization Emergency Operations Centre reports from the Earthquake had the lowest score with an average score of 2.54/17 and the Health Cluster - Cholera reports had the highest average score of 11/17. There is a wide variety and quality of information published in terms of epidemiological information in emergency reports with a distinct difference found between the earthquake reporting and the cholera event. A comprehensive and modifiable template for emergency reporting could alleviate these differences and allow for improved reporting. Citation: Dhillon P, Annunziata G. The Haitian Health Cluster Experience: A comparative evaluation of the professional communication response to the 2010 earthquake and the subsequent cholera outbreak. PLOS Currents Disasters. 2012 Sep 5. doi: 10.1371/5014b1b407653.

Concepts: Public health, Epidemiology, Evaluation, Pandemic, World Health Organization, Cholera, 2010 Haiti earthquake, John Snow