Influenza Epidemic Preparedness Program

Swine Influenza

Swine Influenza

SWINE INFLUENZA frightening you? CONCERNED about the health implications? Coughs and Sneezes Spread Diseases! Stop The Swine Flu from Spreading. Follow the advice to keep your family and friends safe from this virus and not become another victim. These simple cost free guidelines will help you to protect yourself from the swine flu.

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Pandemic Survival

This eBook shows you what it takes to survive the next pandemic. There is no doubt that in the future, the world will be hit with a huge pandemic, either from natural causes or from a terrorist attack. As you look through history, you will be hard-pressed to find any pandemic in history that has killed less than 1 million people. You do not want you or your family to be among those millions. And with the help of the information in this eBook, you have a way to survive the global pandemic that will come. Wishing it won't happen doesn't do anything Preparing for it gives you the tools to survive AND thrive. This book contains the two-pronged approach of John Hartman's years of research in figuring out how pandemics work and living through a dangerous flu outbreak. This gives you the methods to both avoid getting a virus in the first place, and how to strengthen your immune system should you come down with a virus. You don't have to lay down and die. You can fight the next pandemic.

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Dems Sars Hbv Hcv and HIV1

Current methods for the diagnosis of HCC rely on serological markers such as a-fetoprotein (AFP) 97 and certain liver enzymes as well as Des gamma car-boxyprothrombin (DCP) 98 . This type of diagnosis lacks the sensitivity to detect HCC at an early stage when therapy can be more effective. To find markers of disease progression, 2DE was employed to resolve and compare proteins present in serum obtained from individuals infected with HBV or HCV and with varying risks for the development of HCC 99,100 . In several studies, proteins expressed at different levels among diseased individuals as compared to those of healthy ones were identified as markers for disease progression as well as proteins with different N-glycosylation patterns 99-101 . In another study, 2D-MS was also employed to analyze altered plasma proteins due to SARS-CoV infection. Thirty-eight different plasma proteins from SARS patients were identified, most of which were associated with acute phase proteins 23 .

Influenza Has Been Responsible for Some of the Worst Pandemics in History

Neuraminidase And

The influenza virus infects the upper respiratory tract and major central airways in humans, horses, birds, pigs, and even seals. In 1918-19, an influenza pandemic (worldwide epidemic) killed more than 20 million people, a toll surpassing the number of casualties in World War I. Some areas, such as Alaska and the Pacific Islands, lost more than half of their population during that pandemic. The first time a human influenza virus was isolated was in 1934 this virus was given the subtype designation H0N1 (where H is hemagglutinin and N is neuraminidase). The H0N1 subtype persisted until 1947, when a major antigenic shift generated a new subtype, H1N1, which supplanted the previous subtype and became prevalent worldwide until 1957, when H2N2 emerged. The H2N2 subtype prevailed for the next decade and was replaced in 1968 by H3N2. Antigenic shift in 1977 saw the re-emergence of H1N1. The most recent antigenic shift, in 1989, brought the re-emergence of H3N2, which remained dominant...

The virulence of the 1918 pandemic influenza virus unraveling the enigma

The 1918 influenza pandemic caused acute illness in 25-30 of the world's population and resulted in the death of up to 40 million people. Using lung tissue of 1918 influenza victims, the complete genomic sequence of the 1918 influenza virus is being deduced. Neither the 1918 hemagglutinin nor neuraminidase genes possess mutations known to increase tissue tropicity that account for virulence of other influenza virus strains, such as A WSN 33 or the highly pathogenic avian influenza H5 or H7 viruses. Using reverse genetics approaches, influenza virus constructs containing the 1918 hemagglutinin and neuraminidase on an A WSN 33 virus background were lethal in mice. The genotypic basis of this virulence has not yet been elucidated. The complete sequence of the non-structural (NS) gene segment of the 1918 virus was deduced and also tested to determine the validity of the hypothesis that enhanced virulence in 1918 could have been due to type I interferon inhibition by the NS1...

Biology has implications for public policy

Human activities are changing global climates, causing the extinction of a large number of species, and resulting in the spread of new human diseases and the resurgence of old ones. For example, the rapid spread of SARS and West Nile virus was facilitated by modern modes of transportation. Biological knowledge is vital for determining the causes of these changes, for devising wise policies to deal with them, and for drawing attention to the marvelous diversity of living organisms that provides goods and services for humankind and also enriches our lives aesthetically and spiritually.

Plasma cellsB lymphocytes and antibodies

A major focus for those interested in hemorrhagic dengue 55 . Similar questions have been raised for HIV, though more in the context of promoting virus growth and persistence 80 .The structural basis of antibody neutralization is clearly an important focus 8 . More research is being done on antibody neutralization, particularly as attempts are made to develop immunization strategies to limit the ravages of the AIDS pandemic 23, 70 .

Questions terminology and underlying principles

Parasites are ubiquitous in the lives of primates, and infectious diseases can cause devastating mortality in wild populations, including recent deaths arising from Ebola hemorrhagic fever and anthrax infections in African apes (Walsh et al. 2003b Leendertz 2004). An incredible diversity of parasites inhabits primate hosts, including sexually transmitted viruses, insect-borne protozoa that cause malaria, and helminths responsible for schistosomiasis and tapeworm infections. More than 50 different parasite species have been documented in some free-ranging primate species, such as olive and yellow baboons (Nunn et al. 2003a), and an individual primate may shed hundreds or thousands of parasite infectious stages over the course of a single day (Pitchford and Visser 1975 M ller-Graf et al. 1996 Nizeyi et al. 1999). Many of these infectious agents, such as simian immunodeficiency viruses (SIVs), are relatively benign in their natural hosts, and thus have virtually undetectable effects on...

Preface and Introduction

The summer of 2006 marked the 30th anniversary of the outbreak of Legionnaires' disease, an acute pneumonia that occurred among veterans who had gathered in Philadelphia, Pennsylvania, in 1976 to celebrate the bicentennial of the founding of the United States. Ironically, the nation and world were braced for an epidemic of swine influenza, which never materialized and no one expected the emergence of a new bacterial pathogen, since most in the medical field sincerely believed that all the pathogens of humans were now known. This new bacterial agent of Legionnaires' disease, Legionella pneumophila (named in memory of the deceased veterans) was a harbinger of diseases to come (emerging pathogens) that has included HIV AIDS, SARS, Lyme disease, hamburger disease, and many others. The further discovery that L. pneumophila was ubiquitous to aquatic environments worldwide and resided as an intracellular parasite of amoeba and protozoa provided a link between natural environments and human...

Aids As A Medical Problem

The overall shape of the HIV AIDS pandemic in the United States is shown in Figure 8.1. Currently more than 1 million people in the United States are HIV infected or have frank AIDS. Only about a third of those infected are aware they are infected. Three-quarters of affected individuals are male, and half of those are black. Male homosexuals now account for less than half of existing cases. Current estimates for new cases range between 40,000 and 60,000 annually. The HIV AIDS pandemic in the United States. The HIV AIDS pandemic in the United States. yet come close to something like smallpox or hepatitis B as a killer of human beings on a historical scale. It is coming close to, and may have already surpassed, the influenza epidemic that swept 30 million human beings from the face of the earth just after World War I. What is so frightening about AIDS is the speed with which it is spreading, the incredible rate of increase in the number of cases diagnosed each year, with absolutely no...

Historical background

The influenza pandemic of 1918 was exceptional in both breadth and depth. Outbreaks of the disease swept not only North America and Europe but also spread as far as the Alaskan wilderness and the most remote islands of the Pacific. It has been estimated that one-third of the world's population (500 million people) may have become infected and ill during the pandemic 6, 16 . The disease was also exceptionally severe, with mortality rates among the infected of more than 2.5 , compared to less than 0.1 in other influenza epidemics 44, 60 . Total mortality attributable to the 1918 pandemic was probably around 40 million 12, 27, 52 . Unlike most subsequent influenza virus strains that have developed in Asia, the 'first wave' or 'spring wave' of the 1918 pandemic seemingly arose in the United States in March, 1918 1, 12, 28 . However, the near simultaneous appearance of influenza in March-April, 1918 in North America, Europe, and Asia makes definitive assignment of a geographic point of...

Epidemic Models with Population Dispersal

Space structure plays an important role in the spread of a disease. Some epidemic diseases have occurred in some regions frequently and were transmitted to other regions due to population dispersal. For example, SARS was first reported in Guangdong Province of China in November of 2002. The emerging disease spread very quickly to some other regions in Mainland China as well as Hong Kong, Singapore, Vietnam, Canada, etc. In March of 2003, the World Health Organization, for the first time in its history, issued a globally warning about the disease. In late June of 2003, the disease was under control globally, but it had spread to 32 countries and regions causing about 800 deaths and more than 8000 infections (see, for example, Wang and Ruan (2004a)). Hence, it is important to use mathematical models to understand the effect of population dispersal on the spread of a disease. Basically, there are two ways for this purpose. First, we can introduce space variables and use reaction...

Human Immunodeficiency Virus

Human immunodeficiency virus (HIV) is the cause of a worldwide pandemic with estimates that 50-100 million individuals will be infected by the year 2000. (See also Chapter 25.) Although acquired immunodeficiency syndrome (AIDS) is primarily a disease of young persons, elderly persons are also affected and diagnosis is frequently unrecognized (81-83). As of June 1996, 10 of the AIDS cases in the United States were in persons older than age 50 (81). Of these, 28 were over age 60 and 13 were 65 yr and older. Until recently, the primary source of HIV in the elderly was blood transfusion during the period between 1978 and 1985. Currently, the most common risk factor among AIDS patients over age 50 is homosexuality. It is estimated that in the United States, one million homosexuals persons are aged 65 and older (82). Intravenous drug use ranks second and a history of blood transfusion now ranks third as the most common HIV risk factors in older persons (82). In addition, older adults have a...

Viral Evasion Strategies for Antiviral Responses

Ebola virus VP35 protein is another dsRNA binding protein inhibiting RIG-I-mediated signaling (Cardenas et al. 2006). Like NS1 of influenza A virus, VP35 may have dual inhibitory functions in addition to dsRNA sequestration, it may be inhibiting steps downstream of IPS-1and IRF-3 kinases.

The role of reverse genetics systems in determining filovirus pathogenicity

The family Filoviridae is comprised of two genera Marburgvirus and Ebolavirus. To date minigenome systems have been developed for two Ebola viruses (Reston ebolavirus and Zaire ebolavirus ZEBOV ) as well as for Lake Victoria marburgvirus, the sole member of the Marburgvirus genus. The use of these minigenome systems has helped characterize functions for many viral proteins in both genera and have provided valuable insight towards the development of an infectious clone system in the case of ZEBOV. The recent development of two such infectious clone systems for ZEBOV now allow effective strategies for experimental mutagenesis to study the biology and pathogenesis of one of the most lethal human pathogens.

Human Immunodeficiency Viruses

Although the first case of AIDS was described as recently as 1981, the pandemic has escalated at such a rate that by 1993 the World Health Organization (WHO) estimated that over 13 million young adults had been infected with HIV and over 2 million had already developed AIDS, most of whom had died (Fig. 35-3). Approximately 5000 new infections occur every day. By the turn of the century it is projected that 30-40 million will have been infected and that over 1 million will die every year. Moreover, because the principal modes of spread are heterosexual intercourse and perinatal transmission, millions of children will either die from AIDS or be orphaned by the year 2000. In many of the large cities of the United States AIDS is now the commonest cause of death in young adults. However, the situation is even worse in Africa, where 20-30 of the sexually active age group in several cities are already infected, and in Southeast Asia and India, where poverty breeds prostitution and HIV is...

Epidemiology of HIV Infection

These three official patterns are not static, and the distinctions are no longer clear-cut. For instance, the situation in Central and South America was originally comparable to that in the United States, but spread to the heterosexual population has occurred much more quickly. Whereas the classification was invaluable for some years, it is now clear that AIDS everywhere will sooner or later become a heterosexually transmitted disease, with intravenous drug use also making a significant contribution. The principal difference between different geopolitical regions is likely to be socioeconomic AIDS will become increasingly a disease of the poor and underprivileged, as has been their lot with regard to other devastating infectious diseases throughout history. In addition to recognizing the reality of global health interdependence, the wealthier nations will be called on to display a high degree of altruism if the pandemic is to be controlled.

Heterogeneities and dynamical complexities

Dispersal, and potential natural barriers to host movement. Spatial simulations could point to sites for implementing physical barriers or intensive vaccination efforts to slow or stop pathogen spread (Russell et al. 2005). Detailed records of habitat use, spatial distributions, and between-group contact necessary for such simulations already exist for several wild primate species (Waser 1976 Kappeler 1998b Di Fiore 2003 Dias and Strier 2003), and these can be augmented by gene flow estimates derived from molecular data (Gagneux et al. 2001). In other cases, monitoring data that track the spatial spread of novel pathogens like Ebola virus can be used to parameterize models, and thus used to predict where new outbreaks might occur and how fast the pathogen will spread in populations of susceptible hosts.

Cryptococcus Neoformans

Cryptococcus neoformans is an encapsulated fungus that mainly causes infections of the central nervous system in immunocompromised individuals with T-cell defects (e.g., AIDS, lymphoproliferative disorders, immunosuppressive therapy), but which can also infect immunocompetent individuals (Dromer et al., 1996 Mitchell et al., 1995). The incidence of disseminated cryptococcosis has increased considerably in the last decades because of the AIDS pandemic, and still rises in developing areas such as Sub-Saharan Africa and Asia were highly active anti-retroviral therapy (HAART) and anti-fungal therapy are not readily available (Mwaba et al., 2001 Imwidthaya and Poungvarin, 2000 Hajjeh et al., 1999).

Interactions among Biogeochemical Cycles

The 1990 Assessment Report of the Intergovernmental Panel on Climate Change (IPCC) paid little attention to risks to human health. In contrast, IPCC's 1996 Assessment Report gave detailed consideration to the potential effects of climate change on human health. Our increasingly interconnected global society enables disease organisms to travel rapidly around the world, as in the case of the SARS virus, which was carried by infected people from China to Canada within a few days. The combination of human mobility and climate warming poses serious challenges to human health throughout the world.

Host range amplification and arboviral disease emergence

Sylvatic Cycle Arbovirus

In the most extreme example, dengue viruses (DENV-1-4, 4 different viruses) have evolved independently to adopt humans as their amplification and reservoir hosts, resulting in the emergence of tropical and subtropical pandemic disease during the past half century 10, 28 . This review describes examples of mechanisms of arboviral disease emergence and the effect of host range on human exposure and infection, with a focus on mosquito-borne viruses of the New World. Examples are largely drawn from the alphaviruses (Togaviridae Alphavirus) 30 and flaviviruses (Flaviviridae Flavivirus) 8 , which, along with the bunyaviruses (Bunyaviridae) comprise the major taxa of arboviruses 6 .

Conclusions And Prospects

Control of infection by human retroviruses may be achieved by screening of blood donations and pregnant women, by safer sexual practices in the case of HIV, and for those societies that can afford it, anti-retroviral therapy. A vaccine to protect against HTLV-I is achievable scientifically, but without the political or public health will to apply it. Genuinely efficacious, broad specturn HIV vaccines are barely on the horizon. Yet an effective, affordable HIV vaccine is the one factor that could halt the HIV pandemic.

Biological decontamination pathogens and recombinant DNA

The containment of organisms in the higher ACDP categories, such as P4 (Ebola virus, green monkey disease, Lassa fever, etc.), is a specialist subject and is beyond the scope of this book. The bovine spongiform encephalopathy (BSE) agent, or prion, presents some extreme and very challenging decontamination problems, also well beyond this text. Standard isolators are regularly used, however, for the containment of lower category pathogens such as tuberculosis, hepatitis, and HIV.

Ines Colmegna MDa Robert F Garry PhDb

The human genome sequencing project and similar initiatives for other species have revealed that a large portion of vertebrate genomic DNA consists of genetic elements that are present in multiple copies. These repetitive elements can be subdivided into those that are interspersed (transposons and other mobile elements, processed pseudogenes) or tandemly arrayed (satellites and telomeres) in the genome. Human endogenous retroviruses (HERVs) represent a class of interspersed mobile repetitive elements known as retrotransposons. HERVs are closely related to certain members of the Retroviridae, an important family of human and animal viruses that includes HIV and human T-lymphotropic virus (HTLV), causes of the AIDS and adult T-cell leukemia, respectively. Before the pandemic emergence of HIV, the study of this virus family lead to the discovery of onco-genes, a quantum advance in the field of cancer genetics. In contrast to exogenous retroviruses, which are transmitted horizontally as...

Evaluation of Suspected Immunodeficiency

Dihydrorhodamine Test

The clinical utility and capacity to evaluate immunologic function has evolved significantly over the past few decades in parallel with the marked increase in understanding the human immune system (Fleisher and Oliveira 2004). In addition, the expanding range of characterized primary immune deficiency diseases and the secondary immunodeficiency pandemic resulting from HIV have added impetus to the development of new approaches for evaluating immunologic function.

Emerging Infectious Diseases

Young Living Essential Oils Distributors

Cryptosporidium parvum Ebola virus Ebola haemorrhagic fever Pathogens and toxins with potential for use as weapons are called select agents and include bacteria, bacterial toxins, and certain viruses (see table). The threat from such agents depends on both the severity of the disease it causes and the ease with which it can be disseminated. For example, Ebola virus causes a fulminating hemorraghic disease, but Anthrax (Bacillus anthracis) Botulism (Clostridium botulinum toxin) Plague (Yersinia pestis) Smallpox (Variola major) Tularemia (Francisella tularensis) Viral hemorrhagic fevers (filoviruses e.g., Ebola, Marburg and arenaviruses e.g., Lassa, Machupo ) such pathogens as the widely publicized Ebola virus and Legionella pneumophilia, the bacterial causative agent for Legionnaires' disease. Ebola was first recognized after an outbreak in Africa, in 1976. By 1977, the virus that causes this disease had been isolated and classified as a filovirus, a type of RNA virus that includes...

Properties of Filoviridae

Filoviruses replicate well in Vero (African green monkey) cells, as well as infecting guinea pigs, hamsters, and monkeys. Viral replication in the cytoplasm of host cells is marked by the formation of large inclusion bodies, and maturation occurs via budding from the plasma membrane. More detailed studies of the relationships between different filoviruses have been handicapped by the difficulty in developing a virus neutralization test. However, Marburg and Ebola viruses are distinguishable by small differences in genome size and protein profiles, as well as by the absence of antigenic cross-reactivity as determined by antibody-binding assays. There are also consistent differences in tryptic peptide and oligonucleotide fingerprints of the Sudan and Zaire strains of Ebola virus, but strains isolated in different places and in different years in each country are similar. The Ebola-Reston virus, which was initially identified with polyclonal Ebola antisera, reacts with most but not all...

Mathematical Studies of Dynamics and Evolution of Infectious Diseases

The practical importance of understanding the dynamics and evolution of infectious diseases is steadily increasing in the contemporary world. One of the most important mortality factors for the human population is malaria. Every year, hundreds of millions of people suffer from malaria, and more than a million children die. One of the obstacles of controlling malaria is the emergence of drug-resistant strains. Pathogen strains resistant to antibiotics pose an important threat in developing countries. In addition, we observe new infectious diseases, such as HIV, Ebora, and SARS. In Chap. 2, Zhien Ma and Jianquan Li give an introduction to the mathematical modeling of disease dynamics. Then, they summarize a project of modeling the spread of SARS in China by the authors and their colleagues.

Likelihood Markov Computation

The genomics database GenBank has information on about 100,000 species. More than 4 million species of organisms have been discovered and described, and it is estimated that tens of millions remain to be discovered. Placing these species in the Tree of Life is among the most complex and important problems facing biology 45 . Since the mid-1980s, there has been an exponential growth in the number of phylogenetic papers published each year. Recently, the Deep Green consortium achieved a first draft of the phylogeny of all green plants 7, 35 . The Tree of Life project therefore promises to be a substantial, international research program involving thousands of biologists, computer scientists, and mathematicians. The scientific aim is to understand the origins of life, the shape of its evolution, the extent of modern biodiversity, and its vulnerability to existing or possible threats. Indeed, phylogenetic analysis is playing a major role in discovering new life forms. For example, many...

Antigenic Drift and Shift

Antigenic shifts occur following epitope exchanges between humans, animals, and the virus. In the swine flu influenza pandemic, commingling of genetic material from the Hong Kong influenza strain (H3N2) and swine influenza (H3N1) resulted in the new strain that was H3N1.

Genetic Changes in Influenza A Virus

During the past century there have been five pandemics of human influenza, namely in 1890, 1900, 1918, 1957, and 1968 The pandemic at the end of The first clear evidence that distinct mechanisms are involved in the processes of antigenic shift and drift came from peptide mapping and partial amino acid sequencing of HA proteins, which demonstrated relatively close relationships between strains within each of the three human subtypes (HI, up until 1957 H2, 1957-1968 H3, 1968 to the present) but major differences between subtypes, indicating that a sharp discontinuity in the evolutionary pattern had occurred with the emergence of H2 in 1957 and H3 in 1968. With the advent of nucleic acid sequencing it became feasible to determine the complete nucleotide sequence of all eight genes of many strains of influenza viruses isolated from several species of animals and birds. Phylogenetic analysis of the data now indicates that all of the influenza viruses of mammals, including humans,...

Coronavirus Replication and Viral Maturation

The coronavirus genome consists of the longest known, sense RNA strand exceeding 30 kb, which is integrated in the envelope in the form of a helical ribonu-cleoprotein. A hallmark of coronaviral RNA replication is the production of seven subgenomic mRNAs, each of which codes for one viral structural protein. The synthesis of progeny viral RNA takes place in association with specialized membrane structures, characterized as double-membrane vesicles. Viral maturation takes place in the rough endoplasmic reticulum after replacement of cellular proteins by viral proteins in the membranes. The viruses are then transported to the Golgi apparatus. The ensuing virus release mechanism is unknown. Recently, the receptor involved in the entry of the SARS virus into the cell was reported to be the angio-tensin-converting enzyme 2 (ACE2). The SARS virus is transmitted aerogenically with an incubation time of two to 10 days. Clinically, fever and a marked shortness of breath is noted, developing...

Spread of the Black Death in Europe 1347 1350

Black Death Europe 1347

The fascination with the Black Death, the catastrophic plague pandemic that swept through Europe in the mid-14th century, has not abated with the passage of time. Albert The Black Death, principally bubonic plague, was caused by an organism (Bacillus pestis) and was transmitted by fleas, mainly from black rats, to man. It was generally fatal. The article by Langer (1964) gives a graphic description and some of the relevant statistics. The historical article by McEvedy (1988) discusses the pandemic's progress and surveys some of the current thinking on the periodic occurrences of bubonic plague. The plague was introduced to Italy in about December 1347, brought there by ship from the East where it had been raging for years. During the next few years it spread up through Europe at approximately 200-400 miles a year. About a quarter to a third of the population died and approximately 80 of those who contracted the disease died within 2-3 days. Figure 13.2 shows the geotemporal spread of...

Basic Knowledge and Developing Tendencies in Epidemic Dynamics

Infectious diseases have been a ferocious enemy since time immemorial. To prevent and control the spread of infectious diseases, epidemic dynamics has played an important role on investigating the transmission of infectious diseases, predicting the developing tendencies, estimating the key parameters from data published by health departments, understanding the transmission characteristics, and implementing the measures for prevention and control. In this chapter, some basic ideas of modelling the spread of infectious diseases, the main concepts of epidemic dynamics, and some developing tendencies in the study of epidemic dynamics are introduced, and some results with respect to the spread of SARS in China are given. Infectious diseases are those caused by pathogens (such as viruses, bacteria, epiphytes) or parasites (such as protozoans, worms), and which can spread in the population. It is well known that infectious diseases have been a ferocious enemy from time immemorial....

Respiratory Viruses 11 Influenza

Of the viral infections that cause disease in older adults, influenza is recognized as one of the greatest causes of morbidity and mortality. Pneumonia and influenza together comprise the fifth leading causes of death in persons aged 65 yr and older. Influenza viruses are enveloped ribonucleic acid (RNA) viruses that are classified as A, B, or C, based on stable internal proteins (1). The virus contains two major surface proteins, hemagglutinin (H) and neuraminidase (N), which can undergo minor antigenic changes leading to yearly epidemics or major changes resulting in influenza pandemics. Currently, there are two circulating influenza A viruses, H1N1 and H3N2, in addition to influenza B, present in the United States. H1N1 viruses do not appear to cause serious problems in older persons, possibly due to previous immunity (2). Peak influenza activity typically lasts 6-8 wk in a community with attack rates highest in preschool and school-aged children and lowest in older persons. During...

Emerging infectious diseases the publics view of the problem and what should be expected from the public health

The Burden Infectious Diseases 2016

One of the reasons for this disparity has been the actual increase in the number of emerging and reemerging infections that have surfaced during the last 10 years (Box 1). Examples include newly recognized diseases such as hantavirus pulmonary syndrome, new variant Creutzfeldt-Jakob disease, and Nipah and Hendra viral diseases, the introduction and spread of West Nile virus infection in North America, and intermittent outbreaks of Ebola hemorrhagic fever in parts of Africa. Other major concerns include the increasing problems created by antimicrobial resistance and the continued threat of bioterrorism. In 2003 alone, a newly recognized coronavirus spread across five continents sickening more than 8,000 people and causing 774 deaths from a new disease designated severe acute respiratory syndrome (SARS) 4 , the exotic animal trade resulted in the first cases of human monkeypox in the Western hemisphere 5 , and highly pathogenic strains of avian influenza virus killed humans and...

Human Spumaviruses t 561 Further Reading 56l

The novelty and intrinsic importance of retroviruses have been underlined by the award of Nobel Prizes on no less than three separate occasions. The immense significance of the discovery by Peyton Rous in 1911 that a malignant sarcoma of chickens could be transmitted by a cell-free filtrate containing an infectious virus was belatedly recognized by the award of a Nobel Prize in 1966, more than half a century later. Equally controversial initially was the iconoclastic proposal by Howard Temin that genetic information could flow against the tide, from RNA to DNA, which was confirmed unequivocally by the subsequent discovery in 1970, independently by Temin and David Baltimore, of the enzyme reverse transcriptase in retroviruses, for which they received the Nobel Prize in 1975. Among other things, this enzyme has underpinned many of the subsequent spectacular advances in recombinant DNA technology and genetic engineering. Michael Bishop and Harold Var-mus received the Nobel Prize in 1989...

Clinical Features of Influenza

Whereas 80-90 of influenza-related deaths occur in people over the age of 65 (especially over 75), the risk is at least as great for invalids of any age who suffer from chronic conditions affecting the pulmonary, cardiac, renal, hepatic, or endocrine systems. Further, the success of modern medicine in keeping alive so many children with congenital diseases such as cystic fibrosis and immunodeficiencies, and patients of any age with organ transplants or AIDS, has increased the number of younger people at risk of death during an influenza epidemic.

Hemorrhagic Fever Viruses

Hemorrhagic fever viruses (HFVs) are by far the most deadly of human pathogenic microbes. The CDC has designated nine HFVs as potential bioterrorism agents (Table 14.1). We will focus here on only two of these, the Ebola and Marburg viruses (Figure 14.2). Both of these viruses are fairly recent additions to the repertoire of human pathogens, and not that much is known about their interaction with their human host. There have only been a dozen or so outbreaks of these viruses since their discovery in 1967 (Marburg) and 1976 (Ebola). We do not know what animals serve as a reservoir for these viruses hosts that harbor them without contracting serious disease. Several nonhuman primates, such as rhesus monkeys and macaques, are fully susceptible to the ravages of Marburg and Ebola infection and would be unlikely reservoirs. Cases of human infection tend to occur in clusters, the origins of which are not always clear in several instances human infection seems likely to have originated from...

Physiological Side Effects of Cellular Implants

For pig xenografts, proposed as an alternative for human allografts as pig nerve cells (as well as those from other mammals) can integrate and function perfectly to repair the injured brain in other mammals (Huffaker et al. 1989 Isacson et al. 1995 Galpern et al. 1996 Belkadi et al. 1997), screening is needed not only for animal-to-human transmissible diseases but the chances of zoonosis occurring must also be considered. This is a great concern as world wide attention is given nowadays to the fact that not only viruses, but also prions, may jump the species gap (Butler 1998). Large disease outbreaks in humans of the Ebola and Marburg monkey viruses, of the simian-derived HIV AIDS virus and, more recently, of bird flu seem to ward against any use of xenografts in human. Barker et al. (2000) still formulated a series of criteria that should be fulfilled in case pig xenografts are to be used in humans i) microbiological specification of the pig strain, ii) biosecurity of animal...


Korber B, Muldoon M, Theiler J, Gao F, Gupta R, Lapedes A, Hahn BH, Wolinsky S, Bhattacharya T (2000) Timing the ancestor of the HIV-1 pandemic strains. Sci 288 1789-1796 17. Neustadt RE, Fineberg HV (1978) The swine flu affair. US Department of Health, Education, and Welfare, US Superintendent of Documents, Washington DC 22. Sanchez A, Khan AS, Zaki SR, Nabel GJ, Ksiazek TG, Peters CJ (2001) Filoviridae Marburg and Ebola viruses. In Knipe DM, Howley PM (eds) Fields virology, 4th edn. Lippincott Williams and Wilkins, Philadelphia 24. Silverstein AM (1981) Pure politics and impure science the swine flu affair. The Johns Hopkins University Press, Baltimore, Maryland 27. The Chinese SARS molecular epidemiology consortium (2004) Molecular evolution of the SARS coronavirus during the course of the SARS epidemic in China. Sci 303 1666-1669

Mitosis and meiosis

DNA regions can be analyzed and have been shown in Drosophila to contain sequences that are known to be specific for the binding of the enzyme topoisomerase. This finding makes it likely that these regions are the SARs that glue the loops onto the scaffold. The SARs are only in nontranscribed regions of the DNA.


HIV infection has reached pandemic proportions, with life-spans in some underdeveloped nations significantly shortened as a result of widespread infection. As of the end of 1997, an estimated 30.6 million people worldwide have been living with HIV (2). Twenty nine and one half million of those individuals are adults and 1.1 million are children younger than the age of 15 yr. Approximately 41 of HIV-infected adults are women, and trends indicate that this proportion is growing. Worldwide, heterosexual transmission accounts for about 75 of all infections (2). Among children and infants, perinatal transmission accounts for 90 of infections (2). HIV infection rates in underdeveloped countries far exceed rates in developed nations. It is estimated that in 1997 more than 90 of all new HIV infections occurred in developing countries (2). The high rates of infection and mortality in these countries have significantly affected average life-spans. Lack of education, preventative efforts, and...

Finding New Viruses

Viruses (polio, respiratory infections) rabies virus and retroviruses (AIDS, some leukemias). Viruses that infect animals without causing disease may jump species to infect humans or mutate to produce major disease epidemics, such as influenzas from recombinant bird or pig viruses, or the AIDS and Ebola viruses. In some cases, the animal source or reservoir is known, while often it is unknown. Many emerging diseases in human populations have originated in animals native to rain forest jungles or other habitats that humans have invaded and taken over, encountering previously unknown viruses.


Originally introduced in the fifteenth century for the control of plague, quarantine of shipping was used by the English colonists in North America in 1647 to fry to prevent the entry of yellow fever and smallpox. Quarantine proved very effective in keeping Australia free of endemic smallpox, and in delaying the entry of pandemic influenza into that country in 1919. However, with the onset of air travel and the consequent arrival of passengers before the end of the incubation period, quarantine became much less effective. It was re

Lcms Hiv1 and HCV

SELDI ProteinChip SARS, HIV, and hepatitis The SELDI ProteinChip approach has been employed to study the protein profiles of cells infected with viruses, including severe acute respiratory syndrome coronavirus (SARS-CoV), HIV-1, and chronic hepatitis B virus infection (CHB) 31 . SARS is a viral respiratory illness caused by SARS-CoV. SARS was recognized as a global threat in March 2003, after first appearing in Southern China in November 2002 (http 20 ). Current serological methods used for laboratory diagnosis of SARS fail to guarantee early diagnosis since most are based on the detection of antibodies that are produced 17-20 days after the onset of symptoms. ELISA-based antigen detection tests offer high specificity and reproducibility, but they lack sensitivity. On the contrary, PCR-based methods, including reverse transcription-PCR, lack sensitivity and specificity 112 . For this reason, there is a need to develop a diagnostic methodology that can detect SARS...

Select Applications

FAC-MS has been used recently in antiviral development projects to discover two small molecule natural products inhibiting the entry of SARS-Coronavirus into Vero-E6 cells 26 . A range of Chinese herbs (121 different species) were extracted in 85 ethanol and screened via online FAC-MS (using an electrospray TOF instrument), through a column containing the SARS S2 protein. The authors estimate that 130 compounds with Kds under 10 mM were discovered by FAC-MS, and of these hits, two molecules (luteolin and tetra-O-galloyl-b-D-glucose) exhibited low micromolar EC50s in an infection assay using a pseudo-typed virus, correlating well with their highest binding strength in the FAC assay. These two molecules exhibit an activity far superior to glycyrrhizin, another small molecule recently reported to exhibit antiSARS-CoV activity 36 .


Of all the hemorrhagic fevers, Marburg, Ebola-Z, and Ebola-S have the highest case-fatality rates, the most severe hemorrhagic manifestations, and the most pronounced liver necrosis. The pathophysiologic changes are still obscure. There is an early and profound leukopenia, followed by a dramatic neutrophilia with a shift to the left, and very little monocyte infiltration in sites of parenchymal necrosis in the liver, but no unequivocal evidence of disseminated intravascular clotting. Antigen is localized in the liver, spleen, kidney, and adrenal glands, where virus particles can also be seen by electron microscopy.

Clinical Features

Infections of humans with Marburg and Ebola viruses cause similar syndromes, with severe hemorrhages, vomiting, abdominal pain, myalgia, pharyngitis, conjunctivitis, and proteinuria. The onset is sudden, and progress to prostration, profound hypotension, and death is rapid. The mortality rate in the known outbreaks has been very high 25 with Marburg virus, and 60 in the Sudan outbreak and 90 in the Zaire outbreak of Ebola virus infection. However, although several infections of laboratory workers and animal handlers with the Reston virus were recognized serologically, they were not associated with human disease.


Few viruses have played a more central role in the historical development of virology than that of influenza. The pandemic that swept the world in 1918, just as the First World War ended, killed 20 million people more than the war itself. The eventual isolation of the virus in ferrets in 1933 was a milestone in the development of virology as a laboratory science. During the ensuing two decades Burnet pioneered technological and conceptual approaches to the study of the virus in embryonated eggs. His system became the accepted laboratory model for the investigation of viral multiplication and genetic interactions until the early 1950s, when newly discovered cell culture techniques transferred the advantage to poliovirus. Hemagglutination, discovered accidentally by Hirst when he tore a blood vessel while harvesting influenza-infected chick allantoic fluid, provided a simple assay method, subsequently extended to many other viruses. The imaginative investigations of Webster and Laver...


The commonest side effect is a mild local reaction some tenderness, redness, and swelling occur around the injection site in about 15 of recipients. Less frequently fever, malaise, and myalgia may develop within hours and disappear a day later. The only major contraindication for influenza vaccine use is known allergy to eggs though the allergy is rare, inoculation of such persons can produce an immediate allergic reaction. A particularly serious problem, the Guillain-Barre syndrome, was encountered in 1 in every 100,000 Americans vaccinated against influenza A New Jersey 76 (H1N1), during a mass campaign in 1976-77 to protect the population against an outbreak of swine flu which did not spread widely anyway, but no such association has been reported with any previous or subsequent influenza vaccine (see Chapter 9).

Future work

In future work it is hoped that the 1918 pandemic virus strain can be placed in the context of influenza virus strains that preceded and followed it. The direct precursor of the pandemic virus, the first or 'spring' wave virus strain, lacked the exceptional virulence of the fall wave virus strain. Identification of an influenza RNA-positive case from the first wave would have tremendous value in In many respects, the 1918 influenza pandemic was similar to other influenza pandemics. In its epidemiology, disease course and pathology, the pandemic generally was different in degree but not in kind from previous and subsequent pandemics. Furthermore, laboratory experiments using recombinant influenza viruses containing genes from the 1918 virus suggest that the 1918 and 1918-like viruses would be as sensitive to the FDA-approved anti-influenza drugs rimantadine and oseltamivir as are other typical virus strains 76 . However, there are some characteristics of the pandemic that appear to be...

Influenza Virus

Influenza Tran Golgi

Influenza is far more serious than most people appreciate. Although we generally think of 'flu' as no more than an unpleasant (often yearly) experience, new and highly virulent forms arise regularly. Pandemic infections occurred in 1890, 1918, 1957 and 1968 and were associated with very high mortality rates. The influenza pandemic of 1918-1919, for example, killed more people than did the first and second World Wars combined. Within less than 5 months between 20 and 25 million people died, and in some areas entire villages were eliminated (Garrett, 1995). Even the less virulent varieties of influenza can cause considerable morbidity and mortality in the elderly and the young. Three types of influenza viruses (A, B and C) can be distinguished by their nucleoproteins. They vary in the extent to which their surface proteins mutate, with the highest mutation rates being found for the type A virus. As individuals are unlikely to have developed resistance against mutant strains, most...

Types Of Infections

C. neoformans is ubiquitous in the environment and can cause disease in immunocompetent individuals as well as patients with abnormal cell-mediated immunity, especially those with HIV infection, bone marrow stem cell transplants, or hematologic malignancies. The AIDS pandemic has been associated with a dramatic increase in cryp-tococcal infections. C. neoformans has a clear-cut prediction to cause CNS infections and cryptococcal meningitis is the most common invasive mycosis in AIDS, afflicting 5-10 of patients. P. carinii has recently been reclassified as a fungus but clinical management of infections caused by this organism differs significantly from that of other fungi. P. carinii can be found in the lungs of many normal humans, but can cause severe pulmonary and extrapulmonary disease in immunocompromised individuals. Long recognized as a pathogen in malnourished or very premature babies and in patients with marked defects in cell-mediated immunity due to cytotoxic therapy, P....

Other Enteroviruses

Paralysis is usually caused by polioviruses (in the developing world at least), but it has very rarely been associated with coxsackievirus A7. Some outbreaks of enterovirus 71 infection have been marked by meningitis, some encephalitis, and many cases of paralysis with quite a number of deaths. During the 1969-1971 enterovirus 70 pandemic, acute hemorrhagic conjunctivitis was complicated in a small minority of cases by radiculomyelitis, which manifested itself as an acute flaccid lower motor neuron paialysis, resembling poliomyelitis but often reversible. Acule hemorrhagic conjunctwitis burst on the world as a new disease in 1969. Extremely contagious, with an incubation period of only 24 hours, the disease began in West Africa and swept across Asia to Japan, infecting 50 million people within 2 years. As the name implies, this conjunctivitis was often accompanied by subconjunctival hemorrhages and sometimes transient involvement of the cornea (keratitis). Mainly adults were affected....

Influenza Vaccines

Prevention of influenza virus infection by immunization is a formidable task in older persons. Influenza A viruses, the primary cause of severe illness, are classified into subtypes on the basis of their hemagglutinin (H) and neuroaminidase (N) antigens. Sufficient antigen variation or drift within the same subtype, e.g., A Texas 77 (H3N2) versus A Bangkok 79 (H3N2), may occur over time so that infection or immunization with one strain may not induce immunity to related strains of the same subtype. Major antigenic shifts, which herald pandemic influenza, produce new viruses to which the population has no immunity, e.g., the shift in 1957 from H1N1 to H2N2. Influenza B viruses also cause disease in older persons and, although they are much more antigeni-cally stable than influenza A viruses, antigen variation does occur. Consequently, influenza vaccine presently must be administered each year and include the inactivated expected virus strains.