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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


Assessing the mortality impact of the 2009 influenza A H1N1 virus (H1N1pdm09) is essential for optimizing public health responses to future pandemics. The World Health Organization reported 18,631 laboratory-confirmed pandemic deaths, but the total pandemic mortality burden was substantially higher. We estimated the 2009 pandemic mortality burden through statistical modeling of mortality data from multiple countries.

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


BACKGROUND: Geographic variables play an important role in the study of epidemics. The role of one such variable, population density, in the spread of influenza is controversial. Prior studies have tested for such a role using arbitrary thresholds for population density above or below which places are hypothesized to have higher or lower mortality. The results of such studies are mixed. The objective of this study is to estimate, rather than assume, a threshold level of population density that separates low-density regions from high-density regions on the basis of population loss during an influenza pandemic. We study the case of the influenza pandemic of 1918–19 in India, where over 15 million people died in the short span of less than one year. METHODS: Using data from six censuses for 199 districts of India (n=1194), the country with the largest number of deaths from the influenza of 1918–19, we use a sample-splitting method embedded within a population growth model that explicitly quantifies population loss from the pandemic to estimate a threshold level of population density that separates low-density districts from high-density districts. RESULTS: The results demonstrate a threshold level of population density of 175 people per square mile. A concurrent finding is that districts on the low side of the threshold experienced rates of population loss (3.72%) that were lower than districts on the high side of the threshold (4.69%). CONCLUSIONS: This paper introduces a useful analytic tool to the health geographic literature. It illustrates an application of the tool to demonstrate that it can be useful for pandemic awareness and preparedness efforts. Specifically, it estimates a level of population density above which policies to socially distance, redistribute or quarantine populations are likely to be more effective than they are for areas with population densities that lie below the threshold.

Concepts: Demography, Population, Population ecology, Geography, Population density, Pandemic, World population, Overpopulation


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


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


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 effects of influenza on a population are attributable to the clinical severity of illness and the number of persons infected, which can vary greatly between seasons or pandemics. To create a systematic framework for assessing the public health effects of an emerging pandemic, we reviewed data from past influenza seasons and pandemics to characterize severity and transmissibility (based on ranges of these measures in the United States) and outlined a formal assessment of the potential effects of a novel virus. The assessment was divided into 2 periods. Because early in a pandemic, measurement of severity and transmissibility is uncertain, we used a broad dichotomous scale in the initial assessment to divide the range of historic values. In the refined assessment, as more data became available, we categorized those values more precisely. By organizing and prioritizing data collection, this approach may inform an evidence-based assessment of pandemic effects and guide decision making.

Concepts: Public health, Epidemiology, Infectious disease, Influenza, Pandemic, World Health Organization, Epidemic, Syndemic


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


In the new millennium, the centuries-old strategy of quarantine is becoming a powerful component of the public health response to emerging and reemerging infectious diseases. During the 2003 pandemic of severe acute respiratory syndrome, the use of quarantine, border controls, contact tracing, and surveillance proved effective in containing the global threat in just over 3 months. For centuries, these practices have been the cornerstone of organized responses to infectious disease outbreaks. However, the use of quarantine and other measures for controlling epidemic diseases has always been controversial because such strategies raise political, ethical, and socioeconomic issues and require a careful balance between public interest and individual rights. In a globalized world that is becoming ever more vulnerable to communicable diseases, a historical perspective can help clarify the use and implications of a still-valid public health strategy.

Concepts: Medicine, Epidemiology, Disease, Infectious disease, Infection, Influenza, Pandemic, Epidemic


Conflicting recommendations exist related to which facial protection should be used by health care workers to prevent transmission of acute respiratory infections, including pandemic influenza. We performed a systematic review of both clinical and surrogate exposure data comparing N95 respirators and surgical masks for the prevention of transmissible acute respiratory infections.

Concepts: Health care, Medicine, Public health, Epidemiology, Clinical trial, Infectious disease, Influenza, Pandemic