(and other sub-cellular organisms)
Plasmids, Prions, Transposons, Viroids, Virusoids

This is one of a series of literature review documents on pathogenic organisms in water. The series includes documents on protozoans, helminth worms, viruses, fungi, algae, cyanophytes and bacteria. They are meant to list those organisms that may be of concern in water supplies, outline their life cycles, habitats, effects, sources and mechanisms of spread. We need to be aware of the full spectrum of pathogens that are potential contaminants in our water supplies so that we may devise withdrawal protocols or treatment methods to reduce or eliminate the risk to our health. The recommendations presented are those found in the literature, promoted by other jurisdictions or those of the author. These documents are compilations and presentations of information which may be of use in determining orders, codes of practice, policy, recommendations, guidelines or other actions but do not constitute policy, guidelines or recommendations.

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There is an excellent AWWA reference manual which covers many of the same topics as this document which was published and became available to the author after this document was virtually complete. Some material from this AWWA manual has been incorporated into this report where appropriate. The AWWA manual is primarily concerned with drinking water pathogens while this document has a wider scope and deals with all water-borne pathogens which includes those that interfere with recreational, irrigation, industrial and livestock or wildlife uses of water. (AWWA. 1999. Waterborne Pathogens. American Water Works Association. Manual of Water Supply Practices. AWA M48. ISBN 1-58321-022-9).

Current technologies lack the precision and specificity to measure low levels of pathogens on a routine basis and many micro-organisms, particularly viruses and parasites, can escape detection. However, there are recent reports on the possible long-term effects of waterborne viral infections. Enteric viruses, such as Coxsackie B, appear to be associated with heart diseases, in particular myocarditis, an illness which affects the muscular wall. This could be extremely significant, given that most deaths in OECD countries are cardiovascular-related. Enteric viruses infect man and are excreted in the feces in very high numbers thereby having the potential to contaminate drinking water and are spread by the fecal/oral route. They include the enteroviruses, rotaviruses, hepatitis A and E, Norwalk viruses, adenoviruses and reoviruses. Viruses are probably responsible for twice as many waterborne disease outbreaks as Giardia but they are rarely looked for because it is expensive and difficult.

There are a number of entities discussed in this document but there is considerable philosophical and scientific debate as to their status. Which should actually be considered organisms and which are sub-cellular components. They may be parasites or only cellular components. They may be devolved or simplified organisms which have lost some morphology and functionality as they became obligate parasites or they may never have had more structure and function than they have now. From one point of view an independent organism is simply one way for a gene to reproduce itself and these entities may represent other ways for genes to reproduce. Such questions are not the scope of this document, we will simply present all the entities and their modes of transmission. They are also known as sub-cellular life forms which may also be a misnomer.

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These entities lack many of the usually accepted features of life. They do not have cell walls, most of them do not metabolize and they are all parasitic, depending on other cellular organisms for their ability to reproduce. Some of them have no nucleic acid genetic code. Many of them cause diseases, but others are crucial to the well-being of their host and many are so well integrated with their host that it becomes difficult to decide whether they are part of the host or a separate entity. They challenge our notion of organisms as entities with clear, well-defined boundaries. It is clear that life does not respect this simple picture. Whenever a pattern of any sort, however abstract, is able to replicate itself, it does. Typically these patterns overlap and interact in subtle ways, so one can not easily say where one ends and the other begins.

These are the entities being discussed.

Some of these entities are defined in an essay, 'The Recognition of Sub-viral Pathogens', by Diener and Prusiner in Maramorosch and McKelvey-1987. There is considerable discussion and disagreement about the correct classification of these entities. They stretch our concepts of biology, especially evolutionary biology. These entities are small. DNA is a double-stranded helix containing information in the form of AT and CG base pairs, paired molecules of adenosine and thymine, or cytosine and guanine. RNA is a single-stranded helix containing information in the form of A, U, C, and G bases, molecules of adenosine, uracil, cytosine and guanine. The human genome is made of DNA and contains about 5 billion base pairs. The genome of a bacterium is also made of DNA but has less than 10 million bases. The potato spindle tuber viroid is nothing but a circular loop of RNA consisting of 359 bases. Small, simple, but highly effective. Prions do not have any nucleic acid.

Prions do not appear to be spread in any way except by eating infected nerve tissue, generally brain cells. Viruses are well known to spread independently in water in their inert form and cause infections upon injection, ingestion, inhalation or simply contact with body fluids. The other entities are all spread only within their prokaryotic or eukaryotic host cells, accompanying cellular debris or by viruses. In this form they are certainly spread by water and stopping the spread of the cellular debris, bacteria or viruses is the means of preventing the spread of these entities. Often a virus is spread within a bacterium and the other entities inside the virus. In some cases the bacterium is inside a worm or protozoan so one can get multiple diseases all at once. Hospital and slaughterhouse wastes are of the most concern; these should be sterilized before they enter the common sewer trunk lines. Most of the diseases caused by viroids are plant diseases and not of concern in human or animal drinking water but are of concern in irrigation water. Most of the following discussion is concerned with viruses but it should be remembered that the other entities, except prions, may accompany the viruses.

Except for prions, these entities all have a small genome. They replicate, spread and, if appropriate, form particles, in much the same way as the viruses. One could almost say that there is a continuum between naked replicating transmissible RNAs, depender packaged transmissible RNAs, simple viruses and complicated viruses like the herpesviridae and poxviridae. Organelles and obligate cellular bacterial parasites like rickettsiae would seem to represent a different lineage completely, because of the independent capacity for protein synthesis. It is not presently known if viroids and virusoids are the progenitors of modern viruses, have degenerated from other more complicated viruses or some of both. Life is complex and interrelated; the simplistic animal, vegetable or mineral concept has been untenable for a long time.

A plasmid has been defined as a small autonomously replicating circular molecule of DNA that is devoid of protein and not essential for the survival of its host. Plasmids range in size greatly, from about 4350 to 240,000 base pairs. Most known plasmids infect bacteria, but some infect plant and animal cells. They often copy themselves into the DNA of the host cell and many carry genetic traits from one cell to another. Most plasmids have a limit to the number of copies of themselves they maintain in each host, the so-called copy number, which ranges from 1 to about 40. Many plasmids are conjugative. This means they can transfer copies of themselves from one host to another by forcing the host to undergo conjugation, a form of sex in which genetic material is exchanged between bacteria. People tend not to speak of plasmids as life forms quite as often as they do with viruses. This may be, in part, because plasmids are sometimes beneficial to their host cells, rather than pathogenic.

The other type of sub-cellular components that are also called plasmids are the chloroplasts and mitochondria, which are major components of eukaryotic cells. They are essential components for photosynthesis and terminal oxidation and presumed to have arisen as endosymbionts of cyanophytes or blue-green algae. Life is not composed of simple organisms, living things are complex associations or ecosystems.

Some viruses become plasmids when parts of them are missing. For example, the lambda bacteriophage is a virus that infects the intestinal bacterium Escherichia coli, but lambda dv particles, which arise from the lambda phage simply by deleting some DNA are plasmids. The lambda phage multiplies inside its host and then kills it by lysis which destroys the cell membrane and releases lots of copies. The lambda dv particles, on the other hand, stay within the cell in a fairly stable number of copies and do not kill the host. The difference is that while the lambda dv particles contain genes for replication, they lack genes for lysis and the protein coat.

Whether we think of plasmids as life forms or not, we must admit that they are very successful. Many plasmids are spread so thoroughly in cultures of bacteria that less than one cell in 100,000 lacks a copy. Some kinds of plasmids contain genes that help make sure copies are efficiently passed on to both daughter cells when the host cell divides. F plasmids temporarily inhibit cell division when they have not yet replicated inside the host. Plasmids are very diverse; some important kinds include:

Cosmids and Phasmids are man-made entities based on plasmids, used in biotechnology to move desired genes around.

R Plasmids
R plasmids were first discovered in Japan in 1957. In Japan dysentery was treated with sulphonamide until about 1950. However, more and more strains of the bacteria causing dysentery became resistant to this antibiotic rapidly rendering it ineffective. Doctors then began using tetracycline, streptomycin and chloramphenicol. By 1957 2% of the bacteria causing dysentery were resistant to one of more of these drugs and by 1960 13% were resistant. R plasmids were responsible.

R plasmids contain genes that give their bacterial hosts resistance to antibiotics as well as to poisonous metal ions such as arsenic, silver, copper, mercury, lead and zinc. Because many R plasmids are conjugative this resistance can spread from one bacterium to another. Because they can live in more than one species of bacteria R plasmids can also spread resistance between bacteria of different species. Spread of resistance to antibiotics is now a major problem in medicine. Drugs which were used for many years to control bacterial diseases are now becoming useless against new resistant strains. The problem has been made worse by the tendency for people to use antibiotics when they are not strictly necessary, for example as part of livestock food, and to misuse them by not completing a treatment regime. As a result an environment is created where bacteria with resistance have a great competitive advantage so they spread rapidly.

It has also recently been found that weeds growing near crops that were genetically engineered to resist herbicides can acquire this trait. This may well happen via plasmids as well. R plasmids make it clear that the idea of evolution as a battle between species with separately evolving genomes is a great oversimplification. Instead genetic communication and cooperation between different species can be very important.

F Plasmids
F plasmids live in the bacterium Escherichia coli and were discovered in the 1920s. An F plasmid contains genes that make the cell membrane of its host form long tubes. These tubes, called sex pili, attach themselves to other Escherichia coli and puncture their cell membranes. The F plasmid then duplicates and a copy passes from the original host to the new host. The sex pili of a given bacterium never attach to itself. F plasmids give their hosts no known traits besides these sex pili. The evolutionary origins of sex are much debated and we see here the possibility that sex can originate as a kind of disease whose sole function is to spread a parasite.

Colicin Plasmids
Colicin plasmids contain genes that give their host bacterium a certain small probability of bursting open and releasing chemicals called colicins. These chemicals kill other bacteria by rendering their cell membranes permeable to important ions. There are many strains of colicin plasmid. Each one confers immunity only to the particular sort of colicin it produces. Different strains of colicin plasmid are incompatible, meaning that a given strain of bacterium cannot contain both. Different strains of colicin plasmid compete with each other using the resources of their hosts. A colicin plasmid will confer an advantage to its host bacteria if the other strains of bacteria nearby do not have a colicin plasmid. However, when there are many different strains of colicin plasmid present all strains of host bacteria suffer.

Colicin plasmids are not the only sort of plasmids that exhibit incompatibility. Similar plasmids tend to be incompatible with each other while drastically different plasmids are usually compatible. One theory is that incompatible plasmids use the same mechanisms to maintain their copy number. In a cell containing two incompatible sorts of plasmid their reproduction is blocked until the total number of copies of the two together drops to the copy number of each one. This is an unstable situation, especially for plasmids with a low copy number, so eventually descendants of the host cell contain only one or the other plasmid.

Virulence Plasmids
Virulence plasmids contain genes that make their bacterial hosts more virulent. A familiar example involves the bacterium Escherichia coli, which inhabits the human large intestine. Certain strains of Escherichia coli contain plasmids whose genes make the Escherichia coli synthesize toxins that cause diarrhea. These enterotoxigenic strains of Escherichia coli are probably an important cause of diarrhea among travelers. More seriously, in developing countries, diarrhea is one of the principal causes of death among those under five. Vibrio cholerae, the cause of cholera, is a bacterium whose genes code for a diarrhea-causing toxin. The DNA of these genes is closely related to the DNA of certain virulence plasmids infecting Escherichia coli, so closely that there is almost certainly a common ancestor. For example, Vibrio cholerae could have evolved from an earlier bacterium by permanently integrating the DNA from a virulence plasmid into its genome.

Strains of bacteria and viruses often become less virulent as they co-evolve with their hosts. Thus one may wonder what evolutionary advantage a virulence plasmid could confer to the bacteria containing it. In the case of bacteria causing diarrhea there is an obvious possibility, diarrhea can serve as a very efficient mechanism for spreading the bacteria and their plasmids that cause it.

Metabolic Plasmids
Metabolic plasmids contain genes that let their bacterial hosts metabolize or degrade otherwise indigestible or toxic chemicals. For example, the bacteriumPseudomonas putida is able to grow on a wide range of organic compounds that are toxic to most bacteria, including toluene, octane, camphor, naphthalene and nicotinic acid. It does this with the help of genes contained by metabolic plasmids called TOL, OCT, CAM, NAH and NIC plasmids. It is worth noting that all these chemicals are secreted by plants as part of a defense against bacteria. Other metabolic plasmids allow bacteria to degrade herbicides like 2,4-D as well as certain detergents. There is current research on the possibility of using such plasmids to help biodegrade pollution.

Tumor-Causing Plasmids
Crown gall is a cancer of plants caused by a bacterium known as Agrobacterium tumefaciens. Actually, the disease is caused by a plasmid having this bacterium as its host. When the plasmid passes from the bacterium to the cells of infected fruit trees some of the genes contained in the plasmid cause tumors.

Cryptic Plasmids
Cryptic plasmids are plasmids that have no known effect on their hosts. This may be due to our ignorance or being truly cryptic may be a successful strategy.

Cosmids are man-made circular loops of DNA containing plasmid DNA together with an arbitrary sequence of up to 45,000 base pairs of DNA. They are constructed by recombinant DNA techniques and then packaged in lambda phage protein coats. They are used to transfer genes to bacteria. The lambda phage is a virus that specializes in invading bacteria such as Escherichia coli. In nature its protein coat latches onto the bacterial cell membrane and injects the phage DNA into the bacterium. Bio-technologists have taken advantage of this by using the lambda phage protein coat to inject a cosmid into the bacterium. Once inside, the cosmid replicates like a plasmid and like a plasmid integrates its DNA into the genome of the bacterium.

Phasmids are man-made linear DNA molecules whose ends are sequences taken from the lambda phage while the middle is a sequence taken from a plasmid together with a sequence of whatever DNA one wants. Like cosmids, they are constructed by recombinant DNA techniques and packaged in lambda phage protein coats, and used to transfer genes to bacteria. However, both the lambda phage and plasmid replication functions are intact. In particular, they contain the lambda phage genes for lysis, the process whereby a virus dissolves the cell membrane of its host. Depending on the conditions the phasmid can act either like a phage or a plasmid.

Prions are small, proteinaceous infectious particles that contain no detectable nucleic acid of any form but are transmissible among certain animals where they cause fatal brain diseases. These particles are rod-shaped about 165 nanometers long and about 11 nanometers in diameter. They consist largely of a protein called PrPSc, having molecular weight of 33,000-35,000. They are able to resist inactivation by boiling, acid, pH 3-7, ultraviolet radiation, 254 nm, formaldehyde and nucleases. They can be inactivated by boiling in detergents, alkali with a pH > 10, autoclaving at 132 degrees centigrade for over 2 hours and denaturing organic solvents such as phenol.

Stanley Prusiner won the Nobel prize for medicine in 1997 for his work on prions. His theory is that prions are a modified form of a protein naturally occurring in the brain, PrP, and that this modified form can arise from a cell mutation but then spread by means of a kind of auto-catalyzed chain reaction. This theory was initially very controversial because all other self-reproducing biological entities contain RNA or DNA. This is still a controversial topic. In the earlier literature prions are sometimes called slow viruses because of their slow effect, however, no virus has ever been associated with prion diseases.

Prions have recently received a lot of publicity as the cause of mad cow disease, bovine spongiform encephalopathy. Starting in the mid-1980s this disease infected thousands of cattle in England, in part because they were being fed offal containing brain tissue from sheep infected with a prion-caused disease called scrapie. People were worried that eating meat from cows with bovine spongiform encephalopathy could cause a prion-induced brain disease in people. There are already a number of known prion-induced brain diseases in people such as Creutzfeldt-Jakob disease which occurs spontaneously in about one in a million people and kuru transmitted by means of cannibalism among the Fore tribe in New Guinea. There are also known prion-induced brain diseases in mink, cats, deer and moose.

Mice, goats, and sheep develop disease after exposure to the agent that causes bovine spongiform encephalopathy, BSE, or mad cow disease while other animals such as hamsters and chickens do not. These apparently BSE-resistant animals have been assumed to pose no risk for transmitting the disease within their own or to another species. A recent study raises the possibility that resistant animals could act as carriers of the agents that cause BSE or related diseases. Mice were injected with the agent that causes hamster scrapie. Like BSE and its human counterpart Creutzfeldt-Jakob disease, CJD, scrapie belongs to a family of rare, fatal brain diseases known as transmissible spongiform encephalopathies, TSEs. An indication of TSEs is the presence of abnormal prion proteins in the brains of affected persons and animals. For this reason TSEs are also known as prion diseases. Mice are very resistant to hamster scrapie and none of the mice in the RML experiment developed the disease. However, the infectious scrapie agent remained in the brains and spleens of these mice for as long as 782 days after they were injected. Healthy hamsters injected with these infected mouse tissues developed scrapie.

Prions almost certainly do not have a nucleic acid genome. It seems that a protein alone is the infectious agent. A prion has been defined as small proteinaceous infectious particles which resist inactivation by procedures that denature nucleic acids. The discovery that proteins alone can transmit an infectious disease has come as a considerable surprise to the scientific community. Prion diseases are often called spongiform encephalopathies because of the post mortem appearance of the brain with large vacuoles in the cortex and cerebellum. Probably most mammalian species develop these diseases. Specific examples include:

These original classifications were based on a clinical evaluation of a patients family history symptoms and are still widely used. However, more recent and accurate molecular diagnosis of the disease is gradually taking the place of this classification. The incidence of sporadic CJD is about 1 per million per year. GSS occurs at about 2% of the rate of CJD. It is estimated that 1 in 10,000 people are infected with CJD at the time of death. These figures are likely to be underestimates since prion diseases may be misdiagnosed as other neurological disorders.

The diseases are characterized by loss of motor control, dementia, paralysis wasting and eventually death, typically following pneumonia. Fatal Familial Insomnia is an untreatable insomnia and dysautonomia. Details of pathogenesis are largely unknown. Visible end results at post-mortem are non-inflammatory lesions, vacuoles, amyloid protein deposits and astrogliosis. GSS is distinct from CJD, it occurs typically in the 40s and 50s, characterized by cerebellar ataxia and concomitant motor problems, dementia is less common and the disease lasts several years ending in death. It was originally thought to be familial but is now known to occur sporadically as well. CJD typically occurs a decade later and has cerebral involvement so dementia is more common and the patient seldom survives a year. It was originally thought to be sporadic but is now known to be familial as well. FFI pathology is characterized by severe selective atrophy of the thalamus. Alpers syndrome is the name given to prion diseases in infants.

Scrapie was the first example of this type of disease to be noticed and has been known about for many hundreds of years. There are two possible methods of transmission in sheep:

Humans might be infected by prions in 2 ways:

This is one of the features that single out prion diseases for particular attention. They are both infectious and hereditary diseases. They are also sporadic in the sense that there are cases in which there is no known risk factor although it seems likely that infection was acquired in one of the two ways indicated above.

Kuru is the condition which first brought prion diseases to prominence in the 1950s. It occurred in geographically isolated tribes in the Fore highlands of New Guinea. Research established that eating brain tissue of dead relatives for religious reasons was likely to be the route of transmission. The Fore tribe ground up the brain into a pale grey soup, heated it and ate it. Clinically the disease resembles CJD. Other tribes in the vicinity with same religious habit did not develop the disease. It is speculated that at some point in the past one Fore tribe member developed CJD and since brain tissue is highly infectious this allowed the disease to spread. Afflicted tribes were encouraged not to ingest brain tissue and the incidence of disease rapidly declined and is now almost unknown.

Transposons, or transposable elements, or jumping genes are sequences of DNA that move within their host's genome from one position to another. They were first discovered in the 1940s by Barbara McClintock who later won the Nobel prize for this work. They exist in all known organisms often in large quantities. Their main function appears to be simply their own self-replication rather than any benefit to the host or even any direct effect whatsoever on the host phenotype. For this reason people sometimes refer to transposons as selfish DNA.

In addition to transposons, there is plenty of other DNA in our chromosomes that does not seem to code for necessary proteins. This is sometimes called junk DNA. It comes in various distinct forms, such as introns, satellite DNA and pseudogenes. Junk DNA makes up the vast majority of the human genome. There is a fair amount of genetic evidence that transposons spread horizontally between sexually isolated species in addition to being passed vertically down the evolutionary tree. However, the mechanisms of this horizontal transmission are poorly understood. However, certain viruses, the baculoviruses, can pick up and accommodate transposons from their hosts. They have been proposed as a possible mechanism for horizontal transmission of transposons.

The two main classes of transposons are:

Retrotransposons are called Class I elements, while DNA transposons are called Class II elements. There are also Class III elements consisting of transposons that do not clearly fit into the other two categories. Examples include the Foldback elements in fruit flies, the Tu elements in sea urchins and MITEs, or miniature inverted repeat transposable elements, which are found mainly in plants and fungi.

Retrotransposons copy themselves from one location in the host genome to another using an RNA intermediate with the help of reverse transcription from RNA to DNA.

A rough classification of retrotransposons divides them as follows.

LTR retrotransposons are 5000-9000 base pairs long and have long terminal direct repeats, repeating sequences of base pairs at both ends. Between these are the genes needed for transposition, which code for enzymes like reverse transcriptase which copies RNA into DNA, integrase which integrates the DNA into the host chromosome and so on. In all these respects LTR retrotransposons are very similar to retroviruses. The most important difference is that retrotransposons do not code for the proteins forming the viral protein coat. There seems to be some debate as to whether retrotransposons are retroviruses that have somehow lost their ability to code for a protein coat or whether retroviruses are retrotransposons that have somehow gained this ability. The two possibilities are not mutually exclusive.

As the name suggests, non-LTR retrotransposons lack terminal repeats. They have been divided into LINEs and SINEs. LINEs have a characteristic adenosine-rich sequence at one end and are generally 5000-8000 base pairs long though truncated versions are common. They code for various enzymes such as reverse transcriptase and RNase. The genomes of higher animals and plants may have over 10,000 copies of LINEs. In fact, at least 15 percent of the human genome consists of LINEs. SINEs are usually shorter than 500 base pairs. The source of the enzymes needed for the mobility of SINEs is not yet known but perhaps it is LINEs. Higher animals and plants may have over 100,000 copies of SINEs.

DNA transposons
DNA transposons mainly move using a cut-and-paste mechanism. They code for an enzyme called a transposase that catalyzes a process in which the transposon DNA is excised and reinserted elsewhere in the host genome. Thus RNA and reverse transcriptase plays no role in their life cycle.

Viroids and virusoids are unusual infectious agents characterized by having a very small genome. Viroids are common plant pathogens which are a serious economic problem. A viroid is defined to be a small infectious pathogen composed entirely of a low molecular weight RNA molecule. Thus, unlike a virus a viroid has no protein coat. It is nothing but a single-stranded circular loop of RNA. Most viroids consist of about 250 to 575 nucleotide sand are much smaller than a typical virus. Also, viroids do not function as messenger RNAs so they do not make the cell synthesize enzymes. They rely completely on pre-existing enzymes within the host for their reproduction.

The first viroid was discovered in 1971. It is called the potato spindle tuber virus, PSTV, since it causes a disease that makes potatoes abnormally long and sometimes cracked. At the time isolation of the viroid causing this disease met with some skepticism since it was so much smaller than any known virus. By 1991 however, at least 15 plant diseases had been traced to viroids. There are also 2 viroids, the hop latent viroid, HLV and a viroid living in grapevines, that cause no known symptoms. This raises the possibility that there could be more such viroids around.

The complete molecular structure of many viroids has been deciphered, which has allowed a classification of viroids on the basis of their RNA sequences. Roughly speaking there is a large family of viroids that share many features with PSTV, together with one viroid that seems very different, the avocado sun-blotch viroid, ASBV. A further classification of the PSTV-type viroids into three kinds has been proposed. It is clear from these RNA sequences that viroids are not degenerate viruses as had once been thought. They are quite different from any known viruses. One theory is that they arose from RNA that escaped from cell nuclei.

One of the cited websites has a listing of the full nucleotide sequences of all 44 known variants of the potato spindle tuber viroid, it only takes several pages to list the full genomes since they are quite small.

Another several pages at a second site lists all 13 known variants of the Chrysanthemum chlorotic mottle viroid.

Yet another site provides access to the full genomes of a great many viroids which cause plant diseases.

Knowledge of the genetic structure of organisms is growing very rapidly.

All viroid diseases have been detected in the 20th century, some quite recently, in contrast to diseases caused by viruses. Many viroid diseases have been spreading since their discovery often due to human activity. An example is the coconut cadang-cadang viroid, CCCV, a disease of coconuts which has been spreading throughout the Philippines. On the island of Luzon it only affected crops owned by speakers of the Bicalano language while adjacent crops owned by speakers of Tagalog went unharmed. Eventually people realized that the viroids were spread by workers cutting the palms. Tagalog owners prefer to hire Tagalog workers, while Bicalanos hire Bicalanos. Some of the Bicalanos speaking workers came from an area where the disease was prevalent.

Because of this sort of epidemiology viroids may be latent to their native host plants like HLV, becoming pathogenic only when transferred to other species thanks to agriculture. The viroid causing tomato planta macho disease in Mexico, TPMV, has also been found in wild plants. Avocados sometimes seem to recover from ASBV by sending up a new shoot. This new shoot is still infected with the viroid, but it shows no symptoms other than reduced fruit yield. Descendents of such a recovered tree are also infected with the viroid, and are also symptom-less, except for reduced fruit yield. Thus the avocado appears able to come to terms with the viroid in some way. Some viroids may play a beneficial role in their native host plants.

At least 25 different viroid sequences have been determined and numerous variants identified.

  1. Group A-avocado sunblotch viroid, peach latent mosaic viroid.
  2. Group B-Subgroup B1-potato spindle tuber viroid, coconut cadang cadang viroid, tomato plant macho viroid.
  3. Group B-Subgroup B2-citrus bent leaf viroid, pear blister canker viroid.

The RNA genomes of viroids are 246 to 375 nucleotides in length and share many similarities:

The classification described above is based on analysis of the central conserved region, CCR. Group A viroids are clearly distinct. They lack a CCR and possess ribozyme activity. A ribozyme is a catalytic RNA molecule, in this case RNA cleavage is the ribozyme activity. Additionally it is speculated that Group A viroids may replicate in chloroplasts whereas Group B viroids replicate in the nucleus and nucleolus. Three enzymatic activities are required for viroid replication, an RNA polymerase, an RNAse and an RNA ligase.

Group A viroids probably replicate via a symmetric rolling circle mechanism, whereas Group B viroids probably use an asymmetric mechanism. There thus seem to be fundamental differences between the two groups of viroids presumably reflecting different origins. Probably there is more than one mechanism responsible for viroid pathogenesis. Recent evidence suggests that one pathway is due to viroid RNA activating a plant RNA activated protein kinase, or PKR, analogous to the PKR enzyme activated by viral RNAs in mammalian cells. Protein synthesis is reduced and this causes pathogenic effects. In the case of potato spindle tuber viroid, there is a good correlation between the pathogenicity of a strain and its ability to activate PKR in vitro.

Viroid IIa introduced in the first two years of a citrus tree's development reduces tree size, improves yield and fruit size and causes the tree to produce fruit earlier in its life, all characteristics that would be welcomed by citrus producers. Viroid presence in orange trees was discovered less than 20 years ago however, scientists believe they have been present in California for more than a century. Although they were first detected as disease-causing agents, a number of viroids do not cause disease including IIa. Viroids can be found in a wide range of plant species, virtually every grapevine in the world has viroids, however, they do not exist in animals.

To study the effect of certain viroids orange scions from the UC Riverside Citrus Clonal Protection Program that were free of all known pathogens were grafted to Rubidoux trifoliate orange seedlings. At the time of budding the seedlings were also inoculated with single viroid isolates. After growing in a greenhouse for a year they were planted outside. There was little effective dwarfing the first two years but after two to four years in the field, the miniaturizing was evident. After 15 years trees with viroid IIa were strikingly smaller than identical viroid-free trees planted at the same time one row away.

The viroid stresses citrus slightly. Trees, like people, operate a little better under a little stress but not a lot of stress, accounting for the production benefits of viroid-inoculated trees. All trees containing viroid displayed a significant reduction in tree size. Trees with IIa consistently out-yield viroid-free trees by about 15% even though canopy volume is reduced by 20%. Dwarfed citrus trees offer commercial producers the potential benefits of reduced nutrient, pesticide, pruning and harvesting costs. Currently, the most successful dwarfing of citrus trees is accomplished using one particular dwarf rootstock. However, it produces trees 5 to 6 feet tall, too small for commercial production. Another rootstock produces trees about three-quarters as high as full-size 18-foot-tall trees, still bigger than optimal. The viroid may be the key to producing the ideal 8 to 10 foot tall trees.

A virusoid is a viroid-like RNA encapsulated in a virus shell that also contains viral RNA. Like viroids they are circular loops of RNA usually containing about 350 nucleotides. Unlike viroids they reside inside the protein coat of a helper virus. They can only reproduce in cells that have been infected by this helper virus because they use some of the RNA of the helper virus to reproduce. The helper virus is typically an RNA virus consisting of about 4500 nucleotides. A virusoid is a parasite of its helper virus but it is not always so simple. Sometimes the helper virus is unable to reproduce unless the virusoid is present. Now we have symbiosis rather than parasitism between a virus and a virusoid.

The first virusoids were discovered in the early 1980s in Australia associated with viruses causing plant diseases such as velvet tobacco mottle, VTMoV, Solanum nodiflorum mottle, SNMV, lucerne transient streak, LTSV and subterranean clover mottle, SCMoV. One theory about the origin of virsoids is that in plants infected with both viruses and viroids, the viroids got encapsulated in the viruses and then lost their ability to reproduce independently.

The terminology concerning virusoids is confusing. People sometime use satellite RNA as a synonym for virusoid. However, a satellite RNA is defined to be a small RNA that becomes packaged in protein shells made from coat proteins of another, unrelated helper virus on which the satellite RNA depends for its reproduction. The similar-sounding term satellite virus appears to be reserved for an RNA virus that depends for its reproduction on an unrelated helper virus but whose genome codes for its own protein coat.

Virusoids can be spread by vegetative propagation within seeds or by direct inoculation either by insects or man. Virusoids or satellite RNAs are also several hundred nucleotides long circular and single stranded. Virusoids replicate in the cytoplasm using an RNA-dependent RNA polymerase. This enzymatic activity is common in plants but not found in animal cells. They depend on a helper virus for replication. This helper virus also encapsidates them.

There are similar infectious agents which infect animals such as newt satellite 2 transcript. One such agent infecting humans is the hepatitis delta virus, HDV. HDV was first identified in the 1970s in Australia as a nuclear antigen, the delta antigen. Subsequently it was found to be the cause of a particularly virulent form of hepatitis known as type D hepatitis. Common in indigenous natives of South America the method of transmission is not understood but it can be transmitted peri-natally. In the West transmission is associated with drug abuse and transfusion of blood products. It seems prudent to assume that it can also be transmitted sexually. There is no specific treatment.

The delta antigen is associated with a defective pathogen which is obligatorily associated with Hepatitis B helper virus. This virus has a circular single stranded RNA genome of about 1700 nucleotides. It has a ribozyme RNA cleavage activity. This is the smallest known genome for an animal virus. RNA and delta antigen 195 AA are packaged in a Hepatitis B particle. No DNA intermediate has been detected during the replication phase and it is thought that replication occurs by RNA directed RNA synthesis using a DNA dependent RNA polymerase. Certain parts of the genome and the pattern of replication is of course similar to a viroid. One difference is that mRNA and a protein, the delta antigen, are made. These RNAs are nuclear associated and in any case circular RNAs are not good templates for protein synthesis. The fact that the genomic strands are circular probably contributes to the agents stability.

The delta antigen is a nuclear phosphoprotein essential for replication and particle formation. It is basic and associates specifically with the RNA genome thereby stabilizing it. Recently a host protein interacting with the delta antigen has been identified. In fact sequence similarities suggest it is a cellular homologue of the delta antigen. This suggests that it may be able to modulate viral replication. It may also suggest that HDV originated from a viroid like element which then captured a cellular transcript. This was copied into the antigenomic strand and stabilize as part of the genome.


Viruses are a group of infectious agents ranging from 10 to 25 nanometers, nm, in diameter. A virus consists primarily of a genome that replicates itself within a host cell by using its nucleic acids to direct the host cell to synthesize more viral nucleic acids and proteins. Viruses are comprised of highly organized sequences of nucleic acids, either DNA and usually double-stranded or RNA and usually single-stranded, depending on the virus. Viruses have a protein covering which encloses the nucleic acid. Some viruses also have a lipid-rich lipoprotein envelope over the protein covering. The protein or lipoprotein covering determines to what surface the virus will adhere.

A virus may be defined as a small infectious pathogen composed of one or more nucleic acid molecules usually surrounded by a protein coat. They typically reproduce by attaching to the wall of a cell and inserting their genetic material, the nucleic acids, into the cell. This genetic material then uses the enzymatic resources of the cell to make more copies of the virus. Typically these copies multiply within the cell until it bursts. However, the actual life cycle of a virus is often more complicated than this and viruses employ many strategies to overcome the defense mechanisms of the cell.

Viruses have also been defined as entities whose genomes are elements of nucleic acid that replicate inside living cells using the cellular synthetic machinery, and cause the synthesis of specialized elements, virions, that can transfer the genome to other cells. The concept of a virus as an organism challenges the way we define life since viruses do not respire, display irritability, move or grow. However, they most certainly do reproduce and may evolve and adapt to new hosts. If one defines life from the bottom up, that is, from the simplest forms capable of displaying the most essential attributes of a living thing, one realizes that the only real criterion for life is the ability to replicate. As far as we currently know, apart from prions, only systems that contain nucleic acids are capable of this phenomenon. This sort of reasoning leads to a new definition of organisms.

An organism is the unit element of a continuous lineage with an individual evolutionary history.

The key words here are unit element and individual, what you see now as an organism is merely the current occupant of a continuous lineage, the individual evolutionary history denotes the independence of the organism over time. Thus, mitochondria, chloroplasts, nuclei and chromosomes are not organisms, in that together they constitute a continuous lineage, but separately have no possibility of survival, despite their independence before they entered initially symbiotic, and then dependent associations. The concept of replication is contained within the concepts of a continuous lineage and an evolutionary history. Thus, viruses are organisms since:

  1. they most definitely replicate
  2. their evolution can, within limits, be traced quite effectively
  3. they are independent in terms of not being limited to a single organism as host, or even necessarily to a single species, genus or phylum of host.

The likely multiple origins of viruses are unknown resulting mostly from their nature. No one has ever detected a fossil virus as a particle, they are too small and probably too fragile to have withstood the kinds of processes that lead to fossilization or even to preservation of short stretches of nucleic acid sequences in leaf tissues or insects in amber. As a result we are limited to studying viruses that are isolated in the present. The science of virus molecular systematics is, however, shedding a light on the relationships and presumed origins of many important groups of viruses. For example, picornaviruses of mammals are very similar structurally and genetically to a large number of small RNA viruses of insects and to at least two plant viruses and as the insect viruses are more diverse than the mammalian viruses probably had their origin in some insect that adapted to feed on mammals at some point in evolutionary time.

If one were to go back into evolutionary time, a case could be made for descent from a single ancestor of at least the replicase-associated functions of all viruses with positive-sense and negative-sense single-strand RNA genomes. Likewise large DNA viruses like pox and herpes viruses could be presumed to have arisen from cellular organisms given that their enzymes share more sequence similarity with sequences from cells than with other viruses or anything else. Retroviruses, pararetroviruses, retrotransposons and retroposons all probably share a common origin of the reverse transcription function which in turn may be a living relic of the enzyme that enabled the switch from a presumably RNA-based genetics to DNA-based heredity.

Whatever the implications of sequence relationship studies it is apparent that there can have been no single origin of viruses as organisms. For instance, there is no obvious way one can relate viruses with double-stranded linear DNA and 150-300 genes with viruses having single-stranded linear RNA and 4 genes or viruses with single-stranded circular DNA and 3-7 genes. There can be no simple family tree for viruses rather, their evolutionary descent must be considered to be polyphyletic. What they have in common is a role as the ultimate parasites which can only undergo a life cycle inside the cells of a host organism using at the very least the metabolic enzymes, pathways and ribosomes of that host to produce virion components which get assembled into infectious particles.

However, it is apparent that new human viral diseases are still arising at regular intervals and they are often extremely virulent. Examples are those causing Ebola, Marburg and Congo-Crimean haemorrhagic fevers, hantavirus pulmonary syndrome, Korean haemorrhagic disease and HIV1 and 2 (acquired immunodeficiency syndrome, AIDS). These viruses are a great cause for concern internationally and the subject of a great deal of concentrated research. Apart from their intrinsic interest and these new virulent diseases viruses are important because they also cause many common, long-established diseases of domesticated animals, plants and humans such as:

Viruses may be roughly classified into the following 3 types:

The genome of a DNA virus is a single molecule of DNA, either linear or circular, and usually double-stranded. Outside the host cell, this DNA is surrounded by a protein coat. There are several families of DNA viruses affecting humans. The size and structure of the DNA viruses varies widely, from the small hepatitus B virus, HBV, whose round shell contains a circular DNA molecule with about 2,400 base pairs to the large brick-shaped or ovoid pox viruses which have a lipid coating and whose DNA has between 120,000 and 360,000 base pairs. Like retroviruses some DNA viruses work their way into the nucleus of their host cell and then copy themselves into the host's DNA. An example is the hepatitus B virus, which occupies liver cells. This can cause tumors.

The genome of an RNA virus is usually a single molecule of RNA either linear or circular but some contain up to a dozen molecules of RNA. Outside the host cell, this RNA is protected by a protein coat. Most viruses are RNA viruses. There are many families of RNA viruses affecting humans. RNA viruses range widely in morphology and size with their genome containing anywhere from 1,700 to 60,000 nucleotides. The smallest one, the hepatitis delta agent, HDV, is quite different from all the rest. Like a virusoid it is a circular loop of RNA that can only reproduce in cells infected by the helper virus hepatitus B. However, unlike a virusoid it affects animals rather than plants, has its own protein coat and its genome is bigger than that of a virusoid having 1,700 nucleotides instead of a mere 350 or so. Nevertheless, its genome is much smaller than that of any other virus.

One can broadly classify RNA viruses into:

A positive-strand RNA virus consists of single-stranded RNA that functions directly as messenger RNA in the host cell, so that ribosomes in the host cell synthesize various proteins needed by the virus when encountering this RNA. A negative-strand RNA virus consists of single-stranded RNA that does not function as messenger RNA since it contains the complementary base pairs. Negative-strand RNA viruses carry enzymes with them into the host cell to synthesize messenger RNA from the RNA in the virus. Double-stranded RNA viruses have both positive and negative strands. These are more likely to consist of several separate pieces of RNA.

Retroviruses are like RNA viruses when outside the host cell but once inside the nucleus of the cell they can copy themselves into the DNA of the host cell using an enzyme called reverse transcriptase which translates RNA into DNA. They are thus intermediate between RNA viruses and nuclear DNA viruses. Once they are integrated into the DNA of the host cell, they may take a long time to re-emerge. So-called endogenous retroviruses can be passed down from generation to generation indistinguishable from any other cellular gene and evolving with their hosts. The very distinction between host and parasite becomes somewhat blurry in this case. Once an endogenous retrovirus lost the genes that code for its protein coat, it would become indistinguishable from an LTR retrotransposon one of the many kinds of junk DNA cluttering up human chromosomes.

It has been estimated that between 0.01% and 0.1% of the genome of wild and laboratory mice consists of endogenous retroviruses. The same is probably true for humans. Since most mammalian DNA serves no known purpose the above figures may be underestimates. About 97% of human DNA is so-called junk DNA of this sort. Retroviruses are important in genetic engineering because they raised for the first time the possibility that RNA could be transcribed into DNA rather than the reverse. In fact some of them are currently being deliberately used by scientists to add new genes to mammalian cells. In addition, retroviruses are important because AIDS is caused by a retrovirus, the human immunodeficiency virus, HIV. This is part of why AIDS is so difficult to treat. Most usual ways of killing viruses have no effect on retroviruses when they are latent in the DNA of the host cell. Many retroviruses cause tumors in animals. These viruses contain host-derived genetic information.

A number of viral classification schemes can be found in the literature. No attempt has been made to choose one self-consistent and all inclusive scheme since even if one did exist it would no doubt change shortly as more genetic information is gradually acquired through gene sequencing procedures.

There are some basic relationships between picornaviruses, comoviruses and potyviruses and between caulimoviruses, retroviruses and hepadnaviruses. However, no agreement has been reached on family and higher relationships among the viruses. There is a long, complex, key to the identification, not necessarily classification, of viruses at the following web site:

The Baltimore classification scheme is outlined briefly below as an example of a fairly inclusive virus classification based on basic, common characteristics such as genome types and replication strategies. The key above uses the Baltimore classification and keys out the major Baltimore classification groups of viruses before proceeding to identify individual viruses within each classification.

The Baltimore Classification of Viruses

The various types of virus genomes can be broken down into seven fundamentally different groups which obviously require different basic strategies for their replication. Briefly, the types are classified by type of nucleic acid and replication strategy.

DNA Genome Types

Type 1: dsDNA
dsDNA viruses include viruses infecting bacteria and Archaea- phages, and coliphages of Escherichia coli; viruses of higher animals-pox and herpes, adenoviruses and polyomaviruses; viruses of insects-baculoviruses, iridoviruses and polydnaviruses and viruses of eukaryotic algae-phycodnaviruses. They may have circular or linear genomes, have linear genomes which are circularly permuted or linear genomes which have covalently closed ends.

All viruses except polydnaviruses have single-component genomes, the latter have multiple components and the number which constitute an individual genome is not known. Replication of the viruses is in all cases by the semi-conservative method favoured by cellular genomes, however, smaller circular genomes replicate by means of bi-directional replication forks from a single origin like some plasmids. Among the viruses of Eukarya replication mainly occurs in the nucleus, using cellular enzymes such as polymerases and methylases. However, the replication of poxviruses, some baculoviruses, granulosis group and some of the replication of iridoviruses takes place in virus-specified inclusion bodies in the cytoplasm using viral-coded enzymes most important of which are DNA-dependent DNA polymerases.

Type 2: ssDNA
ssDNA viruses include organisms infecting bacteria-bacteriophages, Inoviridae and Microviridae; mammals-circoviruses and Parvoviridae; birds-circovirus-like organisms and plants-Geminiviridae, banana bunchy top-like viruses. They can have linear single-component genomes, circular single-component genomes, circular two-component genomes or circular multi-component genomes. The genomes are all relatively small.

Replication of all of the viruses requires formation of a replicative form double-stranded DNA intermediate. This is formed soon after infection almost certainly by the host cell DNA polymerases engaging in repair of the ssDNA. In the case of circular genomes in Eukarya these get converted into plasmid-like-DNA in the nucleus and become associated with nuclear proteins and complexes such as nucleosomes. Parvoviruses have a strategy for replicating their genomes which uses internal or self-complementarity of genome ends to get around the problem of how to replicate a linear DNA genome.

RNA Genome Types

Type 3: dsRNA
Type 3 viruses include enveloped phages-Cystoviridae; the animal, plant and insect-infecting Reoviridae; the vertebrate and invertebrate infecting Birnaviridae, the Totiviridae which appear limited to primitive Eukarya, fungi and protozoa, though one report describes a virus apparently infecting stinkbugs; Partitiviridae which only infect fungi, and the cryptoviruses which occur in plants but are apparently only transmissible via seed or pollen. The viruses have single-component, two-component, three-component and multi- component genomes. Reoviruses have 10-12 segments of dsRNA per genome, all encapsidated in a single particle.

Type 4: (+)ssRNA

Type 5: (-)ssRNA

Retrovirus Genome Types:

Type 6: diploid ssRNA
The genomes replicate via longer-than-genome-length dsDNA intermediates.

Type 7: dsDNA
The genomes replicate via longer-than-genome-length ssRNA intermediates.

List of Viruses

Virus Descriptions


Picornaviruses are small, 7500 to 8500 nucleotides in length. In the picornaviruses gene expression precedes the replication phase. It is important to note that in eukaryotic cells there is no enzyme that can copy RNA to RNA. Therefore, these viruses are RNA polymerase dependent. All RNA viruses must have their own replicase. Some genera of picornaviruses include enterovirus, hepatovirus, rotavirus, reovirus, cardiovirus, aphtovirus and rhinovirus. No classification would include all of these genera simultaneously since their definitions are not mutually exclusive. Classification at this level is quite unstable and varies from author to author and day to day. Viruses in this group include Coxsackie, ECHO, Foot and Mouth Disease, Hepatitus A, Encephalomyelitis, Encephalomyocarditis and Polio.

Foot-and-mouth disease virus.

Encephalomyocarditis, EMC.

Members of the enteric viruses infect the upper respiratory and gastrointestinal tract of humans and animals, and are excreted in feces. If the feces enter a surface water system, there is potential for the spread of waterborne disease. Enteroviruses have been detected in wastewater, natural water and finished drinking water. Enteric viruses of particular concern in water are the polio, coxsackie and echo viruses. These are tough organisms and can tolerate pH 3 to 5 for 1 to 3 hours, pH 10 to 11 for minutes, all known antibiotics, 70% alcohol, 5% Lysol, ether and other lab disinfectants. They may survive for years in the environment below 5 degrees Celsius.

Humans are the only known natural host but primates and neonate mice can be infected with Coxsackie. There are distinct animal enteroviruses but they do not cross-infect people. Transmission is fecal/oral or respiratory, or by contact for conjunctivitis. Food and water have been implicated. In temperate climates infections peak in late summer, up to 22%, and fall, rates are higher in children and lower socio-economic groups. They are very common and numerous in sewage and any source in contact with sewage, ground water, surface water, marine water, sediments, shellfish, crabs, crops irrigated with wastewater and in animals. Coxsackie and echo virus outbreaks have been linked to swimming pool and beach bathing.

Enteroviruses cause diseases ranging from polio to the common cold. Only several percent of polio infections lead to permanent nerve damage causing paralylis of limbs and the respiratory system. Most cause only stiffness, fever, rash, headache and meningitis. In the early part of the 20th century epidemics in late summer and early fall affecting young children were common. Vaccination has eradicated polio from the western world and it is nearly eradicated in the rest of the world. Coxsackie and echoviruses cause a wide range of diseases, mostly mild or asymptomatic, but more serious effects including myocarditis, diabetes,aseptic meningitis and paralysis do occur with fatality rates under 1%. The incubation period varies from 1 to 35 days. Diseases caused include hand-foot-and-mouth, conjunctivitis, common cold, hepatitis, diarrhea, rash, diabetes, myocarditis, encephalitis, pericarditis, pneumonia, meningoencephalitis, paralysis and other syndromes.

Hepatitus A, HAV, is readily transmitted through water and causes infectious hepatitis an illness characterized by inflammation and necrosis of the liver. Humans are the natural reservoir for HAV. Transmission is through fecally contaminated food, water, body fluids, physical contact. Risk factors include male homosexuality, intravenous drug use, institutional settings, crowding, poor sanitation and hygiene, eating uncooked bivalves, swimming in contaminated water, sewer workers and zoo employees. Waterbourne outbreaks due to contaminated water occur regularly, even in ground water sources. Several hundred thousand cases occur annually in the US; many more in countries with poorer health care, hygiene and water treatment. Normal disinfection practices are not adequate and some prior coagulation/filtration may also be required for complete removal and inactivation.

HAV can be removed from drinking water through coagulation, flocculation and filtration. It generally survives normal sewage treatment processes. HAV is a very resistant virus. It can be inactivated by strong oxidizing agents like free chlorine and ozone or powerful alkylating agents like gluteraldehyde. It is resistant to many proteolytic enzymes, pH's from 1 to 10 for hours, dessication and in water up to 60 degrees Celsius (or 80 if stabilized by divalent cations). HAV persists in the environment for years, especially at lower temperatures.

Infection begins in the gut and moves to the bloodstream and then the liver. Incubation is two to six weeks and symptoms last up to 6 months. Mortality is under 1% unless there are other factors like poor health or immunodeficiency. Most infant and child infections are not symptomatic but the severity of the infection increases with age and most adults have jaundice. Antibodies are formed and subsequent immunity is permanent.

There are both human and cattle rhinoviruses.


Rotaviruses cause acute gastroenteritis especially in children. There are 6 groups of rotaviruses found in humans and animals (monkeys, cattle, sheep, mice, cats, dogs, chickens, turkeys) and cross-infection with animals occurs. Transmission is fecal/oral and likely respiratory as well. They are commonly found in water and wastewater and are known to have caused a number of disease outbreaks due to fecally contaminated water supplies. In outbreaks attack rates may exceed 40%. They resist pH between 3.5 and 10 and survive in nature for weeks, longer at lower temperatures. Like HAV, rotaviruses can be removed from drinking water through coagulation, flocculation and filtration. They are susceptible to free chlorine, ozone and UV.

The incubation period is less than 48 hours and the illness usually lasts up to 8 days. Symptoms include vomiting, abdominal pain, diarrhea, dehydration and fever. Children are the most common victims but adults are also infected. Serious infections occur in children, mostly those under two years old. There are 3.5 million cases and 125 deaths in the US and 500,000 deaths world-wide, annually. Immunocompromised and geriatic patients are also at greater risk of rotavirus infections leading to complications. Large numbers of physician and hospital visits are due to rotaviral infections.


Reoviruses can infect both the intestine and the upper respiratory tract and are found in people, other mammals, birds, reptiles, fish, invertebrates and plants. Human and other mammalian viruses are identical, reoviruses infecting other animals, like birds, are antigenically distinct. Reoviruses have been detected in wastewater, natural water and finished drinking water. They are very widely distributed and are found anywhere fecal contamination has occurred. They survive for years in nature, especially at low temperatures. The are stable down to pH 3.5 and resistant to normal water and wastewater treatment processes. Spread through aerosols occurs and in recreational settings it is not necessary to ingest water, breathing in spray is sufficient, to become infected. Spray irrigation of crops also leads to infection in agricultural workers.


Two species are common in people. Human caliciviruses, including the named strains, Norwalk, Hawaii, Taunton, Snow Mountain and Southhampton, are cosmopolitan viruses and most children have been infected by the time they leave primary school. Hepatitis E is also a calicivirus. Other species infect other animals. Notable among them is the rabbit calicivirus which kills European rabbits in several days.

Classical Caliciviruses
Classical caliciviruses usually affect infants between 1 and 24 months old, though some geriatric cases are found. The incubation period is 48 to 72 hours and the symptoms, usually diarrhea, last 1 (4) to 11 days.

Norwalk Caliciviruses
Norwalk viruses cause acute epidemic gastroenteritis. These strains incubate for 24 to 48 hours and symptoms last 12 to 48 (60) hours. Typically there is vomiting in children but diarrhea in adults. There may also be abdominal pain, cramps, low fever, headache, nausea, malaise and myaglia.It is common in adults and about 40% of US gastroenteritis outbreaks are caused by Norwalk viruses.

Hepatitis E viruses
Hepatitis E causes numerous waterbourne disease outbreaks, generally in monsoon area of the world during the rainy season but also in temperate climates in the autumn. The fecal/oral route is a common means of transmission but shellfish are also implicated. Humans appear to be the main reservoir species but pigs can harbour Hepatitis E. The death rate can reach 14% to 17% (20%) in pregnant women (generally most severe in the third trimester), but is less, 0.1% to 4%, but highly variable for the general population and varies with the outbreak and location suggesting that virulence is strain-dependent. The infection is rarely fatal in normal healthy people but in may be devastating in immune-compromised patients. The incubation period is 2 (5-6) 8 weeks. Children are generally sub-clinical; jaundice typically develops in the 15 to 40 year old patients and lasts for weeks. It is more common is Asian areas. There is no effective treatment.

The virus particles are 70 to 100 nm and there are many known strains which infect a number of other species besides man; man (49), monkeys (27), cattle (10), pigs (4), sheep(1) and dogs (3). Adenoviruses can infect both the intestine and the upper respiratory tract. These normally affect children and cause malaise, fever, cough and nasal congestion. The incubation period is 1 to 3 days. Gastroenteritis may also occur with diarhea and vomiting in infants. Adenoviruses are detected in wastewater and contaminated surface water but not generally in drinking water. Outbreaks of conjunctivitis caused by type 3 and type have been reported in recreational waters and swimming pools. They enter the body via mouth, eye or nose membranes. Human and animal adenoviruses are rarely cross-pathogenic though they apparently are cross-infective since antibodies to cattle, dog and monkey adenoviruses are found in man.


Infection occurs readily in humans, over 70% of people have antibodies by 4 years old, but symptoms, vomiting, diarrhea, gastroenteritis and dehydration are uncommon. Seven serotypes are known. There are no known reservoirs or cross-infections with animals. There are animal species known in dogs and sheep. Transmission is fecal/oral and through water and food. They have been isolated from river water.

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Non-point Source

Viruses may be found in livestock excrement from barnyards, pastures, range lands, feedlots and uncontrolled manure storage areas and in areas of land application of manure and sewage sludge.

-Residential and Urban
Failed on-site wastewater disposal systems can contribute viruses to a water body. Urban runoff may convey viruses from litter and domestic pet excreta.

Viruses in ground water may originate from landfill oxidation ponds and deep well injection of sewage. Other surface water sources include boats that discharge raw sewage overboard, excreta from wild animals in surrounding watersheds and excreta from wildfowl that congregate on the water body.

Point Source

Sewered communities may not have enough capacity to treat the extremely large volume of water resulting from large rainfalls. Periodically treatment facilities may need to bypass treatment of their wastewater. In this case water containing viruses is discharged directly into the surface water body. Estuaries may be particularly susceptible to viral contamination from offshore sewage sludge dumping and offshore sewage pipe outfalls.
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Virus-laden wastewater can either leach into ground water and eventually seep into a surface water body or rise to the ground surface and move to a water body in overland flow. Viruses in overland flow can be transported freely and within organic particles. Water-borne viral diseases may be transmitted to humans in several ways. Viruses are also transmitted in several other ways. Aerosols are a common route responsible for many upper respiratory infections and the fecal/oral route is the usual way intestinal infections are spread. Patients with either type of infection can contribute to waterborne re-transmission of the viruses when body fluids are discharged into water that is not adequately treated to kill or remove viruses. Aerosol-borne infections may be contacted from sneezing or coughing by people with active infections, by bulk air movement from contaminated water during wind or wave action or from cooling towers, air conditioners, humidifiers and other industrial processes where liquid water is unconfined.
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Coxsackie A2 virus survives longer in sewage or in distilled water than in polluted river water, probably due to the lack of predation by other organisms. Enterovirus may remain infective at 4 degrees centigrade for 12 days but loses infectivity in 5 days at 25 degrees. Ground water known to cause infectious hepatitis may still do so after 10 weeks storage. Mediterranean seawater inactivated sabin polio virus-1 in 6 days. The inactivation was not affected by filtration but it was affected by boiling the water first or storing it for several months. Salt solutions had no antiviral effect. Sabin poliovirus-2 was inactivated in 5 days in Vancouver seawater at 25 degrees or 12 days at 4 degrees but lasted 3 months at 17 degrees. There was no loss of infectivity in freshwater.

Certain environmental factors may affect the viability of viruses. Viability is maintained when high levels of suspended sediment in water provides substrates to which the viruses can adsorb. Sorbed viruses may remain nearly 100% viable. Viability decreases when high water temperatures and high sunlight intensity desiccate and inactivate viruses.

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Members of the enteric viruses infect the gastrointestinal tract of humans and may be spread through water. Enteric viruses of particular concern in water are hepatitis A, Norwalk-type viruses, rotaviruses, adenoviruses, enteroviruses and reoviruses. Hepatitus A virus causes hepatitus. Rotaviruses are the primary cause of childhood gastroenteritis and traveler's diarrhea in adults. Adenoviruses may cause eye infections and respiratory disease. Enteroviruses may cause paralysis, meningitis, respiratory illness and diarrhea. The infectious dose of many viruses is very low and the response by the host may vary considerably.

In the table below note that vaccination is a preventive measure, a drug is a treatment for the disease, No indicates there is no control though there may be palliative treatment to extend the life span and/or ease the effects.

Viral Disease Prevention/Treatment
common cold No (pallative)
Coxsackie disease No (pallative)
Dengue fever No (avoid mosquito bites)
Hepatitis A No
Hepatitis B vaccination, interferon, lamivudine
Hepatitis C No, interferon, ribaviron
Hepatitis D No, interferon
Hepatitis E No
Hepatitis G No
Herpes acyclovar (palliative, lifelong infection)
Influenza, flu vaccination (annually, new strains)
Measles vaccination
Mumps vaccination
Poliomyelitis, polio vaccination (almost eradicated)
Rabies vaccination
Rubella, german measles vaccination
Smallpox vaccination (eradicated)
St. Louis encephalitis No (avoid mosquito bites)
Varicella (Chickenpox, Shingles) vaccination (lifelong infection)
Warts (Verruca) No, liquid nitrogen or acid treatment
Western equine encephalitis No, avoid mosquito bites
Yellow fever vaccination
Chickenpox-see Varicella

Common cold
Many viruses cause the common cold. Most colds, 30% to 50%, are caused by one of the more than 100 serotypes of the rhinovirus group. Pinpointing the specific cause of each illness by virus isolation or serologic tests is impractical. The most important determinant of infection is the presence of a specific neutralizing antibody which indicates previous exposure to a virus and offers relative protection. Pathogenic bacteria inhabiting the nasopharynx sometimes cause purulent complications such as otitis media and sinusitis. Bacteria can also cause infections secondary to viral bronchitis.

Onset is abrupt after a short, 1 to 3 days, incubation period. Illness generally begins with nasal or throat discomfort, followed by sneezing, rhinorrhea, and malaise. Characteristically, the illness is afebrile. Pharyngitis is usually present early. Laryngitis and tracheitis with sub-sternal tightness and burning discomfort vary with the individual and with the causative agent. Nasal secretions, watery and profuse during the first day or two of symptoms become more mucoid and purulent, muco-purulent nasal discharge results from the presence of leukocytes. Hacking cough with scanty sputum often lasts into the second week. An exacerbation of persistent bronchitis after a cold is common in people with chronic respiratory tract disease. Exacerbation of broncho-constriction in asthmatics and bronchitic patients frequently occurs with a common cold. Purulent sinusitis and otitis media are usually bacterial complications. When no complications occur symptoms normally resolve in 4 to 10 days.

Clinical symptoms and signs are nonspecific. Bacterial infections, allergic rhinorrhea, and other disorders also cause upper respiratory tract symptoms and at onset, they may be confused with primary coryza. Differentiation depends on the season and the course of the symptoms. Fever and more severe symptoms usually differentiate influenza. Substantial leukocytosis indicates a disorder other than an uncomplicated common cold. Immunity is virus type-specific. Effective experimental vaccines have been prepared for single types of rhino- and paramyxoviruses but the numerous types and strains of known viruses have precluded production of a useful vaccine except for influenza viruses. In controlled trials, large, as much as 2 gm/day, prophylactic oral doses of vitamin C have not altered the frequency of acquisition of rhinovirus common colds or the amount of virus shedding. Hand washing and perhaps use of a disinfectant may be beneficial in an infectious household where most viral respiratory infections are spread. A warm comfortable environment and measures to prevent direct spread of infection are recommended for all persons. Antipyretics and analgesics are commonly used. Antibiotics are not effective against viruses and are not recommended unless a specific bacterial complication develops.

Coxsackie disease (Hand, foot and Mouth disease)
The coxsackie viruses are a group of viruses that are a common source of infection in children. They are transmitted primarily by touch, shaking hands and drinking after someone who has them. Like other viruses the illness caused can be different from one person to another. Coxsackie virus B belong to the same group of enteroviruses as Coxsackie A. While coxsackie B can cause in a very small number of cases a very severe infection of heart muscles, viral myocarditis, coxsackie A only causes mild fever with rashes in the mouth, hands and foot. In viral myocarditis caused by the group B coxsackie virus the heart muscle is affected particularly in neonates. Fever, lethargy/tiredness may be followed rapidly by heart failure with breathlessness and rapid heart rate ending with death due to heart failure. The reservoir for the virus is human.

Coxsackie disease is a viral infection that usually begins in the throat. The throat, tonsils, hands, feet and diaper area are affected by a rash with blisters. The infection commonly affects young children from 2 weeks to 3 years old. The outbreaks occur most often in the spring and fall. This is usually a mild illness with the rash healing in 5 to 7 days. It usually goes away within a matter of days and requires no treatment. Others get what is called herpangina. This is when the virus causes some ulcers in the back of the throat. Children usually complain of a sore throat when this occurs. These symptoms may last from 7-10 days. In addition they may complain of chest pain when they take a deep breath. Finally, there are times when this usually benign virus causes more serious complications involving the heart. Occasionally, the lining around the heart, the pericardium, may get inflamed causing fluid to collect around the heart. When this occurs, the child may be short of breath or have chest pain which is present whether taking a deep breath or not. Complications include possible convulsions with high fever, febrile seizures and a possible nervous system infection, such as viral meningitis or encephalitis. As with many other viruses there are no drugs for this infection. Symptomatic treatment is all that is available.

The most common symptoms include fever, malaise, sore throat, blisters or ulcers in the throat and mouth, headache, a rash with blisters on hands, feet and diaper area and loss of appetite. A physical examination and history of recent illness are usually sufficient to diagnose hand, foot, and mouth disease. Acetaminophen can be used to treat fever. Aspirin should not be used in viral illnesses in children. Ensure an adequate fluid intake because swallowing may be painful. Extra fluid is needed when a fever is present.

Dengue fever
Dengue fever, although little known in North America, is a serious disease of Asia and Africa. Dengue fever occurs in many parts of the Pacific Islands, South and Central America and the Caribbean. In the past 20 years dengue fever transmission and the frequency of dengue epidemics have increased greatly. Classic dengue known for its low mortality but very uncomfortable symptoms has become more serious both in frequency and mortality in recent years. Dengue is caused by an RNA flavivirus exhibiting many serotypes. Symptoms vary according to the serotype. The main vector of dengue, the mosquito Aedes aegypti, flourishes in mankind's urban to suburban environments, and has spread the disease to many parts of the world. Another mosquito, Aedes albopictus, a less important urban vector, has helped maintain the prevalence of dengue in Asian regions.

Aedes aegypti is the most important vector of dengue. The spread of dengue throughout the world can be directly attributed to the proliferation and adaptation of this mosquito. The insect originated in Africa as a mosquito breeding in any temporary puddles of water left by recent rains. The original mosquito proliferated only during high humidity and rain and only the eggs survived when the rain stopped and the puddles evaporated. However, Aedes eggs do need water to hatch. Adults declined as the rains ceased. In short, the adult mosquitoes would bite only during the rainy season. When man invented pottery and urbanized his surroundings the mosquito developed a strain that could breed in man-made containers all year. This new strain of Aedes aegypt became adapted to urban life as people moved away from the proximity of natural water and started to trap water in containers.

Aedes aegypti transmits dengue via bite only. A mosquito feeding on a person who is in the first to fifth day of the disease, can transmit the disease to another person. The dengue virus does not affect the mosquito in any way but an incubation period of 8 to 11 days is required before the mosquito is deemed infective. The insect may be immediately infective after feeding on a host due to the virus present in its mouth parts. Transmission from such mechanical means is a short lived phenomenon. Once infected, the mosquito remains that way the rest of its 15 to 65 day life.

Aedes albopictu, the Tiger Mosquito, considered to be the original vector of dengue, is now a secondary vector. Native to the Asian region it operates as a rural vector of the disease. It may, however, occur in urban areas especially if Aedes aegypti is absent. Its breeding habits are similar to Aedes aegypti, but it appears to exhibit a much broader ecological range. It is strongly attracted to discarded automobile tires. There is some contention that Aedes aegypti is displacing Aedes albopictus in the Asian region. The increase in dengue fever since the 1950s may be correlated with this change in vectors.

Although Aedes albopictus is of lesser importance in the transmission of dengue studies indicate that it is more susceptible to infection than Aedes aegypti. A particular striking dissimilarity with Aedes aegypti is the fact that Aedes albopictus can maintain the disease via trans-ovarial transmission. Males can horizontally transmit dengue to females during mating. Although still unconfirmed some researchers believe that Malaysian monkeys may act as hosts. Some hypotheses suggest that the disease arose from this interaction.

The agent causing dengue is an RNA-containing flavivirus. Four serotypes are known. A serotype refers to how many antigens different viruses have in common. Three disease types may be attributed to these serotypes, classic dengue, dengue haemorrhagic fever, DHF, and a mild dengue. Alternately there are 4 closely related viruses causing dengue fever. Symptoms of classic dengue include fever, severe headache, joint pains, weakness and skin rashes. Classic dengue is not fatal and rarely affects children. Incubation requires five to eight days. The patient is generally very ill for seven days followed by intense weakness for many weeks. DHF causes fever, cough, headache, vomiting and abdominal pain. This persists for 2 to 4 days. Associated with the disease is increased vascular permeability and abnormal blood clotting. Extensive circulatory collapse and internal hemorrhaging may result in death. DHF may lead to dengue shock syndrome, DSS, characterized by nervous disorders such as convulsions. The milder dengue is similar to classic dengue, except that it lasts less than 72 hours.

The reasons for the different forms of dengue is unknown. Related questions about the disease include:

  1. why are children generally unaffected by classic dengue but experience up to 50% mortality with DHF,
  2. why do long-time residents of affected areas generally get DHF,
  3. why do recently arrived individuals contract classic dengue, but not DHF,
  4. why are some individuals immune after exposure.

In general, few deaths were attributed to dengue until the 1950s. Since this time a tremendous increase in DHF relative to classic dengue has occurred in Asia and elsewhere. The reasons for the increase in this form is largely unknown. Some researchers suggests that a more virulent form of the disease developed when Aedes albopictus somehow transferred the disease to Aedes aegypti. This might have occurred if Malaysian monkeys infected with a form of dengue were fed upon by Aedes aegypti. This is not a very well supported hypothesis since outbreaks of DHF have occurred where monkeys are absent. It is interesting to note, however, that only Aedes aegypti and not Aedes albopictus, may vector DHF. A more accepted hypothesis states that DHF is caused by sequential exposures to different serotypes. One variation of the theory suggests DSS is caused by exposure of serotypes 1, 3, or 4 followed a few years later by serotype 2.

Primary infection with type 2 only causes classic symptoms. Type 1 causes DHF. In other words perhaps an individual must suffer classic dengue before getting DHF. Although these ideas are largely unsubstantiated the concept of sequential exposure helps explain some of the aforementioned problems. More research must be performed to determine exactly what synergistic properties these serotypes exhibit and what symptoms these synergies cause.

Currently no dengue vaccine exists. This is not surprising in view of the preceding information. Recent research may yield a vaccine but experts have been saying a vaccine is in the making for the last 25 years. Dengue is definitely a problem of urbanization. Synanthropic mosquitoes such asAed have evolved and vectored the disease to all parts of the world. It is no longer an unpleasant but self-limiting disease. Different forms of dengue cause characteristic unpleasant symptoms as well as a high mortality. The cause of the disease itself requires more studies since it is gradually spreading to different parts of the world and vaccines may not be immediately forthcoming.

Between July 30 and August 11, 2000 the Center for Disease Control and Prevention received three reports from physicians in the United States of cases of dengue fever and dengue hemorrhagic fever, DHF/dengue shock syndrome, DSS, among travelers returning from Bangladesh. All three cases have been confirmed by serologic testing. One of the patients died. According to unofficial reports, in Bangladesh there have been 47 deaths and approximately 2,657 cases associated with the outbreak. Thirty-one of the deaths occurred in Dhaka the country's capital. Dengue hemorrhagic fever has not been previously reported in Bangladesh.

Flu-see Influenza

Hand, foot and mouth disease-see Coxsackie

There are several hepatitis viruses which cause human gastrointestinal distress, impaired liver function and jaundice. Currently hepatitis A, B, C, D, E and G are recognized. Spread is by contact, feces, body fluids, food, milk and water. The disease is much less prevalent where flush toilets and hot running water are available.

Hepatitis A virus, HAV, is classified with the enterovirus group of the Picornaviridae family. HAV has a single molecule of RNA surrounded by a small protein capsid. The term hepatitis A, HA, or type A viral hepatitis has replaced all previous designations such as infectious hepatitis, epidemic hepatitis, epidemic jaundice, catarrhal jaundice, infectious icterus, Botkins disease and MS-1 hepatitis. Hepatitis A is usually a mild illness characterized by sudden onset of fever, malaise, nausea, anorexia and abdominal discomfort followed in several days by jaundice. The infectious dose is unknown but presumably is 10-100 virus particles. HAV is excreted in feces of infected people and can produce clinical disease when susceptible individuals consume contaminated water or foods. Cold cuts and sandwiches, fruits and fruit juices, milk and milk products, vegetables, salads, shellfish and iced drinks are commonly implicated in outbreaks. Water, shellfish and salads are the most frequent sources. Contamination of foods by infected workers in food processing plants and restaurants is common.

Hepatitis A has a worldwide distribution occurring in both epidemic and sporadic modes. About 22,700 cases of hepatitis A representing 38% of all hepatitis cases are reported annually in the US. In 1988 an estimated 7.3% cases were food-borne or waterborne. HAV is primarily transmitted by person-to-person contact through fecal contamination but common-source epidemics from contaminated food and water also occur. Poor sanitation and crowding facilitate transmission. Outbreaks of HA are common in institutions, crowded housing projects and prisons and in military forces under adverse situations. In developing countries the incidence of disease in adults is relatively low because of exposure to the virus in childhood. Most individuals 18 and older demonstrate an immunity that provides lifelong protection against re-infection. In the US the percentage of adults with immunity increases with age from 10% for those 18-19 years of age to 65% for those over 50. The increased number of susceptible individuals allows common source epidemics to evolve rapidly.

The incubation period for hepatitis A which varies from 10 to 50 days is dependent upon the number of infectious particles consumed. Infection with very few particles results in longer incubation periods. The period of communicability extends from early in the incubation period to about a week after the development of jaundice. The greatest danger of spreading the disease to others occurs during the middle of the incubation period well before the first external symptoms. Many infections with HAV do not result in clinical disease especially in children. When disease does occur it is usually mild and recovery is complete in 1-2 weeks. Occasionally the symptoms are severe and convalescence can take several months. Patients suffer from feeling chronically tired during convalescence and their inability to work can cause financial loss. Less than 0.4% of the reported cases in the US are fatal. These rare deaths usually occur in the elderly. All people who ingest the virus and are immunologically unprotected are susceptible to infection. Disease however, is more common in adults than in children.

The virus has not been isolated from any food associated with an outbreak. Because of the long incubation period the suspected food is often no longer available for analysis. No satisfactory method is presently available for routine analysis of food but sensitive molecular methods used to detect HAV in water and clinical specimens should prove useful to detect virus in foods. Hepatitis A is endemic throughout much of the world. Major US epidemics occurred in 1954, 1961 and 1971. Although no major epidemic occurred in the 1980s the incidence of hepatitis A in the US. increased 58% from 1983 to 1989. Foods have been implicated in over 30 outbreaks since 1983. The most recent ones and the suspected contaminated foods include:

Hepatitis B, HBV is a mostly double-stranded DNA virus in the Hepadnaviridae family. HBV causes hepatitis in humans and related viruses in this family cause hepatitis in ducks, ground squirrels and woodchucks. The HBV genome has four genes that encode the viral DNA-polymerase, envelope protein, pre-core protein and an unknown protein 'X' which may be involved in the activation of host cell genes and the development of cancer. Although relatively rare in the United States, hepatitis B is endemic in parts of Asia where hundreds of millions of individuals may be infected. HBV is transmitted horizontally by blood and blood products and sexual transmission. It is also transmitted vertically from mother to infant in the peri-natal period which is a major mode of transmission in regions where hepatitis B is endemic. The blood supply in developed countries has been screened for HBV for many years and at present transmission by blood transfusion is extremely rare. Major routes of transmission among adults in Western countries are intravenous drug use and sexual contact. The risk of HBV infection is notably high in promiscuous homosexual men but it is also transmitted sexually from men to women and women to men. Transmission is probably prevented by correct use of condoms. Health care workers and patients receiving hemodialysis are also at increased risk of infection. Effective vaccines are available for the prevention of HBV infection. All individuals at risk for infection should be vaccinated.

HBV causes acute and chronic hepatitis. The chances of becoming chronically infected depends upon age. About 90% of infected neonates and 50% of infected young children will become chronically infected. In contrast, only about 5% to 10% of immunocompetent adults infected with HBV develop chronic hepatitis B. In some individuals who become chronically infected, especially neonates and children, the acute infection will not be clinically apparent. Acute hepatitis B can range from sub-clinical disease to fulminant hepatic failure in about 2% of cases. Many acutely infected individuals develop clinically apparent acute hepatitis with loss of appetite, nausea, vomiting, fever, abdominal pain and jaundice. In cases of fulminant hepatic failure from acute HBV infection, liver transplantation can be life-saving. About 90% to 95% of acutely infected adults recover. About 5% to 10% of acutely infected adults become chronically infected.

The natural history of chronic HBV infection can vary dramatically between individuals. Some will develop a condition commonly referred to as a chronic carrier state. These patients, who are still potentially infectious have no symptoms and no abnormalities on laboratory testing. Nonetheless, some of these patients will have evidence of hepatitis on liver biopsy. Some individuals with chronic hepatitis B will have clinically insignificant or minimal liver disease and never develop complications, others will have clinically apparent chronic hepatitis. some will go on to develop cirrhosis. Individuals with chronic hepatitis B, especially those with cirrhosis but even so-called chronic carriers, are at an increased risk of developing primary liver cancer. Although this type of cancer is relatively rare in the United States it is the leading cause of cancer death in the world primarily because HBV infection is endemic in the East.

Chronic infection with HBV can be either replicative or non-replicative. In non-replicative infection the rate of viral replication in the liver is low and serum HBV DNA concentration is generally low and hepatitis Be antigen is not detected. In replicative infection the patient usually has a relatively high serum concentration of viral DNA. Patients with chronic hepatitis B and replicative infection have a generally worse prognosis and a greater chance of developing cirrhosis and/or carcinoma. In rare strains of HBV with mutations in the pre-core gene replicative infection can occur. Diagnosis of hepatitis B is confirmed, and prognosis is assessed by liver biopsy. Most people who are chronic carriers generally have little or no inflammation on biopsy. Some individuals with chronic hepatitis B will have various degrees of liver inflammation on biopsy. Others will have fibrosis or cirrhosis. The amount of inflammation and the presence of fibrosis or cirrhosis correlate with a worse prognosis.

Hepatitis C, HCV was discovered in 1989. HCV is a positive, single-stranded RNA virus in the Flaviviridae family. The genome is approximately 10,000 nucleotides and encodes a single polyprotein of about 3,000 amino acids. The polyprotein is processed by host cell and viral proteases into three major structural proteins and several non-structural protein necessary for viral replication. Several different genotypes of HCV with slightly different genomic sequences have since been identified that correlate with differences in prognosis and response to treatment. Despite the discovery of HCV by molecular biological methods and the sequencing of the entire genome a cell culture system for propagating HCV has yet to be established. A non-primate animal model also does not exist. As a result, the production of specific drugs against HCV has been impeded although excellent diagnostic methods for have been developed.

Approximately 4,000,000 people in the United States are infected with HCV. The virus is transmitted primarily by blood and blood products. The majority of infected individuals have either received blood transfusions prior to 1990 or have used intravenous drugs. Sexual transmission between monogamous couples is rare but HCV infection is more common in sexually promiscuous individuals. Peri-natal transmission from mother to fetus or infant is also relatively low, less than 10%, but possible. Many individuals infected with HCV have no obvious risk factors. Most of these persons have probably been inadvertently exposed to contaminated blood or blood products. About 85% of individuals acutely infected with HCV become chronically infected. Hence, HCV is a major cause of chronic hepatitis. Once chronically infected the virus is almost never cleared without treatment. In rare cases HCV infection causes clinically acute disease and even liver failure, however, most instances of acute infection are clinically undetectable.

The natural history of chronic HCV infection can vary dramatically between individuals. Some will have clinically insignificant or minimal liver disease and never develop complications. Others will have clinically apparent chronic hepatitis. Of these, about 25% will go on to develop cirrhosis. About 20% of individuals with hepatitis C and cirrhosis will develop end-stage liver disease. Cirrhosis caused by hepatitis C is presently the leading indication for liver transplantation in the United States. Individuals with cirrhosis from hepatitis C are also at an increased risk of developing carcinoma. A major problem in discussing prognosis in patients with chronic hepatitis C is that it is difficult to predict who will have a relatively benign course and who will go on to develop cirrhosis or cancer. One fairly clear factor for progression to cirrhosis is alcohol abuse. Certain findings on liver biopsy can also be helpful in predicting a relatively benign or progressive course. Viral genotype may also play a role. Additional research is urgently needed to identify host factors that are important in determining prognosis in chronic hepatitis C.

All patients with chronic hepatitis C should be evaluated for possible treatment. In general adults less than 70 years old with evidence of active inflammation on liver biopsy and without advanced cirrhosis are good treatment candidates. Indications for treatment of patients with very mild disease are less clear. Such individuals should be considered for possible participation in clinical studies. Patients with advanced cirrhosis secondary to hepatitis C should be referred to a liver transplantation center. Considerable research is also devoted toward new therapies for chronic hepatitis C.

Hepatitis D virus, delta virus, is a small circular RNA virus. The hepatitis D virus is replication defective and cannot propagate in the absence of another virus. In humans, hepatitis D virus infection only occurs in the presence of hepatitis B infection. Hepatitis D virus infection is transmitted by blood and blood products. The risk factors for infection are similar to those for hepatitis B virus infection. The hepatitis D virus most often infects intravenous drug users. A patient can acquire hepatitis D virus infection at the same time as they are infected with the hepatitis B virus or at any time after acute hepatitis B virus infection. Hepatitis D infection should be suspected in a patient with chronic hepatitis B whose condition suddenly worsens. There is usually an obvious history of continued exposure to blood or blood products, active intravenous drug user. A particularly aggressive acute hepatitis B infection could suggest hepatitis D co-infection. Interferon-alpha is used to treat patients with chronic hepatitis B and hepatitis D infections.

Hepatitis E Virus, HEV, has a single-stranded polyadenylated RNA genome of approximately 8 kb. The disease is clinically indistinguishable from hepatitis A disease. Symptoms include malaise, anorexia, abdominal pain, arthralgia and fever. The infective dose is not known. Diagnosis of HEV is based on the epidemiological characteristics of the outbreak and by exclusion of hepatitis A and B viruses by serological tests. Confirmation requires identification of the particles by immune electron microscopy in feces of acutely ill patients. HEV is transmitted by the fecal-oral route. Waterborne and person-to-person spread have been documented. The potential exists for food-borne transmission. Hepatitis E occurs in both epidemic and sporadic-endemic forms, usually associated with contaminated drinking water. Major waterborne epidemics have occurred in Asia and North and East Africa. To date no US. outbreaks have been reported.

The incubation period for hepatitis E varies from 2 to 9 weeks. The disease is usually mild and resolves in 2 weeks. The fatality rate is 0.1-1% except in pregnant women. This group is reported to have a fatality rate approaching 20%. The disease is most often seen in young to middle aged adults 15-40 years old. Pregnant women appear to be exceptionally susceptible to severe disease and excessive mortality has been reported in this group. HEV has not been isolated from foods. No method is currently available for routine analysis of foods.

Major waterborne epidemics have occurred in India, 1955 and 1975-1976; USSR, 1955-1956; Nepal, 1973; Burma, 1976-1977; Algeria, 1980-1981; Ivory Coast, 1983-1984; in refugee camps in Eastern Sudan and Somalia, 1985-6 and most recently in Borneo, 1987. The first outbreaks reported in the American continents occurred in Mexico in late 1986. To date no outbreak has occurred in the US but imported cases were identified in Los Angeles in 1987. There is no evidence for immunity against this agent in the American population. Thus, unless other factors such as poor sanitation or prevalence of other enteric pathogens are important the potential for spread within the US is great. Good sanitation and personal hygiene are the best preventive measures.

Hepatitis G virus. In 1995 and 1996, several novel human RNA viruses were identified and partially characterized. They can apparently cause acute and chronic hepatitis. These new viruses are related to but distinct from the flavivirus hepatitis C. Three viruses have been termed GB-A, GB-B and GB-C. GB-A and GB-B are likely tamarin viruses, GB-C can infect humans. The genomic sequences of these viruses have been determined. Based on genomic sequences another virus termed hepatitis G virus, HGV, is probably the same as GB-C. The precise role of HGV/GB-C in human disease is currently under investigation, however, most experts now feel that this virus is not responsible for clinically significant cases acute or chronic hepatitis.

Genital herpes simplex is caused by a virus known as Herpes simplex. It affects millions of people causing painful blisters and sores in and around the genital area. Genital herpes is generally spread from an infected person to another by sexual activities, including oral and anal sex. It can be spread even if blisters and sores are not visible. Herpes is not selective, anyone can become infected. People who are sexually active with multiple partners, especially those who do not use a condom, are at the highest risk.

There are painful, fluid filled blisters or sores which will burst in 10-21 days becoming small, painful ulcers. Lymph nodes in the groin area may enlarge and urination may be painful especially in women. There is a burning, tingling or itching in the genital area, discharge from the genital area of males and females, fever and body aches. Sometimes there are cold sores around the mouth.

Treatment may be an oral, topical or intravenous medication. Today the most commonly prescribed medication is acyclovir. Medication only eases the symptoms of herpes and does eliminate the actual virus. Herpes is not curable, the virus will remain in the body permanently. However, it is treatable. There is a risk of passing herpes to the baby during a vaginal delivery. The herpes virus may play a role in development of cervical cancer.

Influenza (Flu)
Until the advent of AIDS influenza was the last uncontrolled pandemic killer of humans. One historic measure of influenza's potential lethality is that more people died in the 1918-1919 influenza pandemic than in World War I. In the United States, influenza currently causes more morbidity and mortality than AIDS. In non-pandemic years, 10,000 to 20,000 people die of influenza-related illness in the US. In pandemic years such deaths can exceed 100,000. Morbidity of course far exceeds mortality.

Influenza or flu which is an RNA viral infection of the respiratory tract is highly contagious and occurs mainly in the late fall, winter or early spring in North America. Influenza is spread from person-to-person through mists or sprays of infectious respiratory secretions caused by coughing and sneezing. Influenza affects all age groups and causes moderate to severe illness, loss of school and work, and complications such as pneumonia, hospitalization and death. Over 90% of the deaths occur in persons aged 65 years and older. Pneumonia and influenza together are the 6th most common cause of death in the United States.

Influenza epidemics may be severe and lead to considerable illness and death. A global epidemic or pandemic of influenza A in 1918 caused over 20 million deaths worldwide and 500,000 deaths in the United States. Other pandemics occurred in 1957 and 1968. The 1968 Asian influenza pandemic caused over 50,000 deaths in the United States and cost over 3.5 billion dollars in medical costs and lost work days. Symptoms include fever, up to 104░ F, chills, sometimes shaking, muscle aches and pains, sweating, dry cough, nasal congestion, sore throat, headache, malaise and fatigue.

There are three types of influenza viruses, influenza A, B and C. Influenza A can infect humans and other animals while influenza B and C only infect humans. Influenza C virus causes a very mild illness and does not cause epidemics. Influenza B virus usually causes a minor illness, but it does have the potential to cause more severe disease in older persons. Influenza A virus, however, causes pandemics. The reason for the recurrent outbreaks is that the virus undergoes periodic antigenic shifts in its two outer membrane glycoproteins, N and H, thus introducing a new virus into a population that has no protective serum antibody. This antigenic drift is an ongoing process and is one way the virus stays one step ahead of the immune system responses of the host. Immunity to one strain of influenza virus does not necessarily confer immunity to a new strain which has undergone antigenic drift. This is one reason why annual influenza vaccination is necessary to protect against the newly circulating strain of influenza virus. Another reason for annual influenza vaccination is that the vaccine induced antibody levels decrease a few months after vaccination offering less protection against subsequent infection.

In contrast to the minor antigenic drift described above major shifts in the influenza A viruses can also occur through other genetic mechanisms. These shifts can occur unpredictably and can lead to serious national epidemics or global epidemics called pandemics. Many different types of animals including humans, swine, birds, horses, aquatic mammals and others may become infected with influenza A viruses. Some influenza A viruses are unique to a particular type of animal and will not normally infect a different type of animal. However, some influenza A viruses may infect several different types of animals. Influenza A viruses which can infect birds, particularly migratory water fowl, swine and humans are thought to be an important cause of major shifts in the influenza A virus. For example suppose a swine becomes infected with an influenza A virus from a human and at the same time becomes infected with a different influenza A virus from a water fowl. When the two different viruses reproduce in the swine the genes of the human strain and fowl strain may mix, resulting in a new unique pandemic virus. This process is called genetic re-assortment. The close proximity of humans, birds and swine that exists among some farming communities in southern China enhances the possibility for this type of virus gene mixing.

Measles is one of the most easily spread infections and is a serious disease. It is caused by the measles virus. The illness starts with a runny nose, watery eyes, cough and high fever. After 2 or 3 days tiny white spots appear in the mouth. After 2 more days a raised red rash starts on the face and spreads down the body and out to the arms and legs. The rash usually lasts 4 to 7 days. Symptoms start about 10 days after exposure and last from 1 to 2 weeks. It is contagious for 1 week before and 1 week after the rash appears. Measles is sometimes complicated by ear infections, pneumonia or encephalitis, inflammation of the brain, which can lead to convulsions, deafness or mental retardation. Measles can cause miscarriages or premature delivery in pregnant women.

Measles is spread by infected droplets during sneezing or coughing, contact with contaminated objects or direct contact with nasal or throat secretions of infected persons. Measles can be prevented through vaccination. Measles vaccine is usually given to toddlers when they are 12 to 15 months of age and then again at 11 to 12 years of age. The measles vaccine is often combined with the vaccines for mumps and rubella. People who have measles should limit their contact with others. People exposed to someone who has measles should consult their health care provider immediately. If they have not been vaccinated measles vaccine can help prevent infection if it is given within three days of exposure. Immune globulin may also help if it can be given within six days of exposure.

Mumps is a contagious infection that causes pain and swelling in glands that produce saliva for the mouth, especially the parotid glands in the cheek. Mumps is caused by a virus that spreads in the nasal fluids, saliva and urine of infected persons. Before a mumps vaccine was developed most cases of mumps happened in children younger than 15 years old. Now mumps tends to cause epidemics on college campuses usually among young adults who have not received the mumps vaccine rather than a result of lost immunity.

Although the mumps virus begins its attack on the body by affecting the glands the virus can easily enter the blood and spread to other body organs. This may cause many different types of complications. In children one common complication is meningoencephalitis which is an infection that attacks brain cells. In boys mumps can also attack the testicles causing pain and swelling and sometimes leading to decreased fertility in about 13 percent of cases. Mumps can cause complications that affect the ovaries, pancreas, kidneys, joints and eyes. It is also an important cause of one-sided hearing loss since it can attack the nerve that carries sound messages from the ear to the brain.

Once a person has been exposed to someone with mumps it can take 14 to 24 days for symptoms of mumps to begin. Symptoms may start with fever, muscle aches, neck pain, headache and a general sick feeling. Next the parotid glands in the cheeks begin to hurt and swell. Swelling fills up the cheeks and the space at the angle of the jaw and pushes the ear lobe upward and outward. While swelling may occur on both sides it is not uncommon for only one side to swell. Swelling occurs rapidly, within hours, but it may take 1 to 3 days for the swelling to reach its peak. It gradually lessens over the next 3 to 7 days. Because the salivary glands are affected eating or drinking certain foods may make gland pain worse. Sour liquids like orange juice and lemonade are especially painful. In many people other groups of salivary glands around the mouth and neck may also be attacked by the mumps virus. This can cause pain and swelling under the jaw, under the tongue or on the roof or floor of the mouth.

In boys, when mumps infects the testis symptoms usually start within 8 days of the cheek swelling. The boy may have a fever, chills, headache and nausea with pain and swelling of the testicles. In seven out of 10 boys only one testicle is affected. Symptoms usually last for about 4 days. Testicular damage as a result of infection is reported in 30 to 40 percent of cases, resulting in a reduction in fertility of 13 percent but rarely absolute infertility. Seven percent of females report pelvic pain and tenderness but there is no evidence of impaired fertility. Organ involvement including pancreas, kidneys and heart, is uncommon but can occur. There is no antibiotic or antiviral medicine to treat mumps.

Caused by a virus, poliomyelitis affects the nervous system and can cause total paralysis in hours. Symptoms include fever, headache, fatigue, stiff neck and pain in the extremities. Irreversible paralysis usually takes place in 1 in 200 cases. As many as 10 percent of those infected die when breathing muscles are paralyzed. The disease is most prevalent in children under the age of 3. Man is the reservoir and discharges viruses in feces and pharyngeal secretions. Transmission is generally by direct contact but the virus can be recovered from rivers and sewage. Polio is due to be eradicated from the earth by 2005 in a mass effort by WHO much like the previous successful effort to eradicate smallpox.

Polio has probably caused paralysis and death for most of human history. The oldest clearly identifiable reference to paralytic poliomyelitis is an Egyptian stele or stone engraving over 3,000 years old. Cases of poliomyelitis tended to be rare in ancient times though as sanitation was generally poor. With improvements in waste disposal and the widespread use of indoor plumbing in the 20th century, epidemics of polio began to occur with regularity in the developed world primarily in cities during the summer. Because sewage was dumped away from the drinking water supply babies were much less likely to be infected with polio and gain protective immunity. As the children got older and began playing with others, swimming in public pools and going to school they were more likely to be exposed to the virus which was then more likely to cause paralytic poliomyelitis.

Though the virus only paralyzes about 1% of the individuals it infects, most infections are asymptomatic or result only in a self-limiting diarrhea, it tends to be transmitted very easily under the right conditions. One percent of all children in a large city translates into thousands of cases and the emotional and economic impact of such epidemics was staggering.

By the time of the Great Depression paralytic poliomyelitis was perhaps the most feared disease known. Polio struck fast, there was no cure and it crippled its victims for life. Hobbling on crutches, rolling in wheelchairs or lying immobile in giant iron lungs the sufferers accumulated from year to year. Even the exact mechanism of polio's transmission was a hotly debated subject for many years so many areas were placed under strict quarantine when cases of the disease began to manifest themselves. Only the fear surrounding AIDS can rival the feelings people had about polio in the first half of this century.

President Franklin Roosevelt declared a War on Polio during his administration and the tremendous resources of postwar America were brought to bear on the problem of developing a vaccine. From the beginning of this effort it was clear that such a vaccine was at least theoretically feasible as contrasted with such pathogens as malaria and HIV where no such assurance exists. In the early 1960s the work bore fruit first with the Salk vaccine and soon after with the Sabin virus strains.

Salk used chemical and heat treatment to kill poliovirus then injected this inactivated virus into patients. The proteins of the destroyed virus taught the immune system of the patient to recognize polio and they were then protected from subsequent infection. The Sabin approach was to grow the virus in the laboratory under a variety of conditions allowing it to accumulate mutations. Ultimately this resulted in an attenuated virus which could be given to a patient orally. The weaker virus replicates normally in the intestine but cannot grow well enough to invade the central nervous system. Once again the immune system learns to recognize polio and this confers protection.

Once the Sabin and Salk vaccines were proven effective the disease was rapidly eradicated throughout most of the industrialized world. The economic effect has been enormous. It has been calculated that the polio vaccine pays for the costs of its development approximately every three weeks. The benefit to the United States alone for this single breakthrough runs into the trillions of dollars. The social impact has been incalculable. The crutches, wheelchairs and iron lungs of polio victims have at last been banished in the developed world.

Rabies virus causes an acute encephalitis in all warm-blooded hosts including humans and the outcome is almost always fatal. Although all species of mammals are susceptible to rabies virus infection only a few species are important as reservoirs for the disease in nature. In the United States several distinct rabies virus variants have been identified in terrestrial mammals including major terrestrial reservoirs in raccoons, skunks, foxes and coyotes. In addition to the terrestrial reservoirs for rabies several species of insectivorous bats also serve as reservoirs for the disease.

Transmission of rabies virus usually begins when the infected saliva of a host is passed to an uninfected animal. Various routes of transmission have been documented and include contamination of mucous membranes, eyes, nose, mouth, aerosol transmission and corneal transplantations. The most common mode of rabies viral transmission is through the bite and virus-containing saliva of an infected host.

Following primary infection the virus undergoes an dormant phase in which it cannot be easily detected within the host. This phase may last for several days or months. Investigations have shown evidence for direct entry of virus into peripheral nerves at the site of infection as well as evidence for indirect entry after viral replication in non-nervous tissue muscle cells. It is during this time that host immune defenses may play a role in the outcome of viral infection because rabies viral antigens are good simulators of cell-mediated immunity. The uptake of virus into peripheral nerves is important for a progressive infection to occur.

Following uptake into peripheral nerves rabies virus is transported to the central nervous system, CNS. Typically this occurs via sensory and motor nerves involved at the initial site of infection. The incubation period is the time of exposure to onset of clinical signs of disease. The incubation period may vary from a few days to several years but typically lasts 1 to 3 months. Dissemination of virus within the CNS is rapid, with early involvement of limbic system neurons. Active cerebral infection is followed by the passive centrifugal spread of virus to peripheral nerves. The amplification of infection within the CNS occurs through cycles of viral replication and cell-to-cell transfer of progeny virion. Centrifugal spread of virus may lead to the invasion of highly innervated nerve sites of various tissues, including the salivary glands. It is during this period of cerebral infection that classic behavioral changes develop.

The first symptoms of rabies in people may be nonspecific flu-like signs, malaise, fever or headache which may last for days. There may be discomfort at the site of the bite progressing within days to symptoms of cerebral dysfunction, anxiety, confusion and agitation progressing to delirium, abnormal behavior, hallucinations, and insomnia. The acute period of disease typically ends after 2 to 10 days. Once clinical signs of rabies appear the disease is nearly always fatal and treatment is typically supportive. Disease prevention is entirely prophylactic and includes vaccination. Non-lethal exceptions are extremely rare with only six documented cases of human survival from clinical rabies but each included a history of either pre- or post-exposure prophylaxis.

Rubella (German measles)>br> Rubella is also called German measles. When children are infected it is usually a mild disease. Rubella also strikes adults and outbreaks can occur among teenagers and young adults who have not been immunized. Rubella usually occurs in the winter and spring and spreads very easily. People catch it through contact with other people who are infected. It is spread through coughing, sneezing or talking.

Usually rubella causes a slight fever which lasts for about 24 hours and a rash on the face and neck that lasts two or three days. Young adults who get rubella may get swollen glands in the back of the neck and some pain, swelling or stiffness in their joints, arthritis. Most people recover quickly and completely from rubella. However, the greatest danger from rubella is not to children or adults but to a fetus. If a woman gets rubella in the early months of her pregnancy her chance of giving birth to a deformed baby may be as high as 80%. These babies may be born deaf or blind, they may have damaged hearts or unusually small brains, many are mentally retarded. Miscarriages are also common among women who get rubella while they are pregnant. The last big rubella epidemic was in 1964. As a result of that epidemic about 20,000 babies were born with severe birth defects. We can protect mothers and their babies from the tragic effects of rubella in two ways. One is to make sure that women are immune to rubella before they become pregnant. This keeps them from getting rubella while they are pregnant and protects their unborn children. The second way is to immunize all children. This protects the children themselves, but it also protects others. Children who can not catch rubella can not spread the disease to their mothers or to other pregnant women.

Shingles-see Varicella


Smallpox is a disease that is caused by a virus. The virus spreads when an uninfected person comes in direct contact with a sick person and breathes in the virus. Usually the virus is in tiny drops coughed up by the sick person. After about two weeks which is the incubation period of the smallpox virus the infected person develops a high fever and muscle aches and pains. After about three days of fever the person breaks out in a rash all over their body. At first it looks like red spots, but these spots gradually became blisters about the size of a pencil eraser. After about 5 days of rash, the fluid in the clear blisters turns to pus. The more pus spots, pustules, that a person has, the more likely they are to die.

There are two main types of smallpox virus, variola major which kills about 20 percent of the infected people and variola minor which kills about 2 percent of its victims. If the person does not die the pus gradually dries up to form scabs that drop off after 1 or 2 weeks. The pustules on the face often leave permanent scars known as pockmarks.

Smallpox was known to the ancient peoples of China, India and Egypt. Pharaoh Ramses V died of it in 1157 BC. It spread wherever large numbers of people moved and it was a particularly serious problem in cities where people lived close together. It first reached Europe in the fifth century and it was one of the leading causes of death in the 16th and 17th centuries. It was brought to the Americas many times during that period, first by the Spanish conquerors and later by African slaves, where it wiped out many native American populations.

Milkmaids spent a lot of time around cows which are carriers of cowpox a virus similar to the smallpox virus. In 1796 the British physician, Edward Jenner, after noting that milkmaids were immune to smallpox, demonstrated that if he infected the skin of someone with the scab of a cowpox sore that person would not get smallpox. This was the beginning of vaccination. During the next 130 years the practice of vaccination was gradually adopted by health workers in all parts of the world but the disease still persisted in many places where not enough people were vaccinated.

In 1965, the World Health Organization, WHO, began a world-wide effort to eradicate smallpox. Studies by epidemiologists showed that the disease could be stopped from spreading if the people who came in contact with infected persons were all vaccinated. The WHO eradication strategy was not to try to vaccinate everyone in the world but rather to find all of the cases as soon as they developed their rashes and then to vaccinate all the people living in the areas where the cases lived. This plan worked well and the disease was completely eradicated from the earth by 1977.

Today the smallpox virus exists only in two freezers in Moscow, Russia, and Atlanta, Georgia, in the United States. If the virus got out it could infect people because people are no longer being vaccinated. However, the viruses are very carefully guarded. Scientists are currently debating whether these frozen viruses should be destroyed or kept for possible scientific and medical research.

St. Louis Encephalitis
Saint Louis encephalitis, SLE, is a mosquito-borne disease. Humans infected with the virus can develop encephalitis which is an inflammation of the brain tissue. This disease is sometimes called sleeping sickness or summer flu. The virus was first identified from victims of a 1933 epidemic in St. Louis, Missouri. The encephalitis mosquitoCulex tarsalis is the primary vector of SLE virus in California. This mosquito becomes infected while feeding on a bird that is infected with the virus. Once infected a mosquito can transmit the virus to other birds, humans or wild life. The natural cycle of virus transmission in nature involves mosquitoes, birds and other animals. Humans can be severely affected by the virus but are dead end hosts because not enough virus develops in their blood to infect other mosquitoes. An SLE infection can be sub-clinical, acute, or fatal. The majority of SLE cases are mild sub-clinical infections. Symptoms of infection appear 7 to 21 days after a bite from an infected mosquito. SLE has three separate syndromes, febrile headache, aseptic meningitis and encephalitis.

In California cases are most likely to occur during the months of May through November. In southern California they can occur almost any month but are more likely during the warmer months. Statewide approximately 80% of the cases occur during August and September. All age groups are susceptible to the disease but children under 9 are less likely to become ill than the elderly. Severity of the disease is age dependent. The fatality rate for individuals under 40 is less than 5% but for the elderly it ranges between 15 to 23%. Other viruses such as measles and mumps or certain other infections can also cause encephalitis. The greatest risk of mosquito bites occurs during the first few hours after sunset. Some ways to reduce the risk of mosquito bites are:

Since 1945 sporadic SLE epidemics have occurred in California the largest involving 99 cases in 1954. Human cases are widespread in California. Historically, the Sacramento and San Joaquin valleys are regions with the highest incidence of human cases.

Varicella (Chickenpox, Shingles)
Chickenpox or varicella is a disease affecting most children in the United States before their 10th birthday. Until recently it could not be prevented only treated. Today children can be immunized against chickenpox. The chickenpox vaccine can protect children against a severe case of chickenpox and prevent the discomfort and possible serious complications the disease can cause. Chickenpox is one of the most common childhood diseases. It is usually mild and not life-threatening to healthy children. The most obvious sign of chickenpox is a skin rash that develops on the scalp and body, then spreads to the face, arms, and legs over a period of 3 to 4 days. The rash forms between 250 to 500 itchy blisters that dry up into scabs 2 to 4 days later. School-age children often get a mild fever for 1 or 2 days before the rash appears. Other symptoms of chickenpox are coughing, fussiness, loss of appetite and headaches.

Chickenpox can easily be spread by direct contact with an infected person usually through fluid from broken blisters, through the air when an infected person coughs or sneezes and through direct contact with lesions or sores from a person with shingles. A person with chickenpox is contagious from 1 to 2 days before the rash starts and for up to 5 days after the rash appears. An adult or child who has never had chickenpox is at risk of getting it and may not show symptoms for 10 to 21 days after being exposed to the virus. Within households 80% to 90% of at-risk persons will develop chickenpox if they are exposed to a family member who has it. Before the vaccine became available there were about 4 million cases of chickenpox in the United States each year. Anyone can get chickenpox at any age but it occurs most frequently in children from ages 6 to 10. Chickenpox can occur at any time of the year. Peak times are in the winter and early spring especially in moderate climates.

If one scratches the blisters before they are able to heal they can become infected turn into small sores and possibly leave scars. Aacetaminophen, a substitute for aspirin, may help reduce fever. Do not use aspirin or salicylate which has been associated with Reye's syndrome a disease that affects the liver and brain. If the fever lasts longer than 4 days, rises above 102░ F after the third day of having chickenpox or there is dehydration see a physician. A physician should be consulted if the rash gets very red, warm or tender. It may mean there is a secondary bacterial infection which needs other treatment. The drug acyclovir can help make a case of chickenpox less severe. Acyclovir is most often used for patients who are at risk of developing severe chickenpox such as adolescents, children with certain skin or lung diseases and children taking other prescribed medications such as steroids. To be effective acyclovir must be given within the first 24 hours of the onset of the chickenpox rash.

Most healthy children who get chickenpox will not have any complications from the disease. However, each year in the United States about 9,000 people are hospitalized for chickenpox and about 90 people die from the disease. The most common complication from chickenpox is a bacterial infection of the skin. The next most common problems are pneumonia and encephalitis an infection of the brain. The following groups of people are at higher risk of developing these problems:

When an adult gets chickenpox, the disease is usually more severe often developing into pneumonia. Adults are almost 10 times more likely to be hospitalized for chickenpox than children under 14 years of age, and adults are more than 20 times more likely to die from the disease. If a pregnant woman gets chickenpox her unborn baby may have complications.

Once someone has had chickenpox the virus stays in the body of the infected person permanently. Later in life the virus can reappear and cause shingles. Shingles can occur at any age but usually occur after a person is 50 years old. About 10% to 20% of all people who have had chickenpox develop shingles. People with shingles typically feel numbness and itching or severe pain in the skin areas where the affected nerve roots are. Within 3 to 4 days clusters of blister-like sores develop and last for 2 to 3 weeks.

Verruca-see Warts

Warts (Verruca)
Warts and verrucas are small thickened growths on the skin, which are caused by a virus. They have a rather rough surface and can be unsightly. They do not usually hurt although they may itch. Warts may affect any part of the body but are most commonly seen on the hands. Warts on the feet are known as verrucas. Here the pressure from the body weight causes them to be flatter and to grow into the skin more. This can cause pain rather like walking on a dried pea. Sometimes people have many warts or verrucas while others only have one or two.

The virus that causes warts and verrucas may be acquired from direct contact or in swimming pools or changing rooms but warts and verrucas do not spread rapidly through a family and it seems to be a question of being more susceptible at certain times in life. Warts will heal on their own given long enough but this may take years. If treatment is needed there are a number various possibilities. Various paints and applications which contain one or more acids and sometimes other chemicals can be used. It is important to rub down the area with a pumice stone or emery board once or twice a week as the skin tends to heap up protecting the underneath part of the wart or verruca. Liquid nitrogen can be used to freeze the wart or verruca. The area may be painful and red for a few days after being frozen but the wart or verruca has usually gone. Sometimes more than one application is needed. Genital warts need a specific type of treatment and the care of a physician. They can be spread to sexual contacts so unprotected sex should be avoided until they have been treated.

Western equine encephalitis
Western equine encephalitis, WEE, virus was initially isolated from sick horses in 1930 and from a fatal human case in 1938. This virus causes an acute febrile illness in equines and humans characterized in its most severe form by signs and symptoms of inflammation and injury of the meninges, brain and spinal cord. Large outbreaks occurred in the north central United States in 1941 and in the Central Valley of California in 1952 and both sporadic cases and small epidemics continue to occur throughout the western states. While the exact number of equine cases is generally not known, it can be conservatively estimated that for every reported human case there are several hundred horse cases. The occurrence of human disease is always associated with equine encephalitis in the same area and equine outbreaks precede the appearance of human cases. In areas where most horses have been vaccinated against WEE, this early warning of viral transmission may be less obvious.

Western equine encephalitis occurs in the early and mid-summer with the incidence being higher in the rural population than in the urban residents. About one-third of the reported cases are in children under 5 years of age, infants under 1 year of age are most susceptible to develop severe encephalitis. Among the reported adult cases, the rates are higher in males than in females, probably because of greater exposure to infected mosquitoes during agricultural and recreational pursuits. Infection is often abortive or undifferentiated and there is a fairly low fatality rate of 3-4 percent.

The incubation period is usually 5 to 10 days. The onset of the illness is sudden especially in adults or characterized by a 2-4 day period of lethargy, fever and headache especially in children. The acute illness is characterized by a spectrum of symptoms and signs referable to the central nervous system reflecting infection and inflammation of the meninges and brain tissues. Fever, sleepiness, headache, anorexia, vomiting and stiff neck are the most common features of an acute infection. The acute phase lasts 3-10 days after which recovery begins suddenly and proceeds rapidly. Recovery is generally complete with rare instances of permanent neurological symptoms. However, about half of the affected infants suffer permanent damage including progressive retardation and major motor disorders.

Western equine encephalitis virus is maintained in a primary enzootic transmission cycle involving wild birds and culicine mosquitoes. In the western United States, the temporal and spatial distribution of WEE is restricted to the distribution and abundance of its known vector the mosquito Culex tarsalis. While Culex tarsali can be found breeding in a wide variety of standing water habitats ranging from stagnant sewage ponds to unattended swimming pools this mosquito is most closely associated with the distribution of irrigated farm and ranch lands where the impoundment or ditching of irrigation waste water forms its prime breeding sources. Seasonal abundance ofCulex tarsalis is latitude dependent but in Southern California the highest populations occur in the Spring and Fall. However, fairly substantial population levels can be found during the Summer and active breeding populations can be found throughout the Winter months.

Many studies have incriminated Culex tarsalis as the vector of WEE in the western United States and Canada. Wild birds serve as the basic viral reservoir hosts during the epidemic season. Both nestling and adult birds of many species serve as effective viremic hosts, some species, such as the house finch and house sparrow appear to play especially important roles. Domestic fowl develop viremias sufficient to infect Culex tarsalis, but probably contribute relatively little to viral amplification. Some mammals, especially jackrabbits, appear to be involved in transmission cycles in certain areas. The overwintering mechanisms of WEE are not completely understood although several theories and modes have been investigated. Among those overwintering mechanisms suggested are: viral reservoir in hibernating arthropod vectors or vertebrates, viral reservoir in local avian species and viral reintroduction by migrating birds. Horses and humans are dead end hosts for WEE virus, viremia levels are insufficient to serve as a source for viral infection.

Yellow fever
Yellow fever is an acute infectious disease characterized by sudden onset of fever, chills, head, back and muscle pain, nausea and vomiting. These may progress to jaundice and haemorrhagic signs. Death usually occurs 7-10 days after onset of illness, following a period of remission on the third or fourth day. During epidemics the case-fatality rate may exceed 50% for un-immunized adults and 70% for children The agent which causes yellow fever is a mosquito-borne virus which is involved in two transmission cycles. In jungle yellow fever transmission occurs between forest-dwelling mosquitoes and non-human primates while in the urban cycle transmission is between domestic mosquito species, especially Aedes aegypti, and man. Humans may acquire the infection through the bite of an infected jungle mosquito and return to an urban area where they become ill 3 to 6 days later. An Aedes mosquito feeding on such a person may initiate an outbreak of urban yellow fever.

Members of the enteric viruses infect the gastrointestinal tract of mammals.

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For human consumption the maximum contaminant level goal, which is rarely if ever achieved or enforced, is zero viruses per 100 ml sample of drinking water. The actual maximum contaminant level, MCL, is generally whatever level the best available technology can achieve with the available source water. Since many of the other entities along with the viruses are often present in cellular debris from asymptomatic organisms including people there should be strict control of the discharge of this material to ambient waters or sewers unless it is sterilized first. Slaughter houses and hospitals are the prime sources of such material. This sterilization must inactivate nucleic acids and denature proteins in order to remove the risk of disease transmission from viroids, virusoids, viruses and prions. Since these entities are found in wildlife that live in watersheds all water should be filtered. It may require coagulation/flocculation first to aggregate the smaller particles and then sterilized before distribution. These are small particles, much smaller than bacteria, so sub-micron filtration is required or else a membrane process is needed to ensure that only water passes.
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The use of coliform indicators to predict virological water quality is not acceptable since the behaviour and fate of animal viruses differs markedly from those of coliforms or coliform indicators. There is no correlation in their numbers. Viruses can be isolated from potable water that has been tested as bacteriologically safe to drink. Viruses are more resistant to sewage treatment processes, environmental conditions and drinking water treatments than coliforms. Polioviruses in sewage require up to 20 mg/L for only a 99.9% kill rate and can be isolated from finished drinking water with turbidity below 1 NTU and free chlorine residual over 1 mg/L. No bacteria are present under these conditions. Viruses passing through treatment plants have chlorine resistance several orders of magnitude higher than na´ve viruses and repeated exposure to sub-lethal chlorine doses leads to more resistant strains in only a few generations. Modern water treatment processes have little effect on removing the threat of viral diseases. The best sewage treatment processes reduce viral densities by a maximum of about 104 however viral densities are usually orders of magnitude greater than this and the infectious doses are in the range of 100 to 102. Viruses can be removed from drinking water through coagulation, flocculation and sub-micron filtration. Reverse osmosis and other membrane technologies will also remove viruses.
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Paper Internet
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Evidence suggests that a prion is a modified form of a normal cellular protein known as PrPc encoded by a single exon of a single copy gene. This protein is found predominantly on the surface of neurones and is protease sensitive. It is thought to be involved in synaptic function. The modified form of PrPc which may cause disease, the prion, is known as PrPsc, for scrapie, which is relatively resistant to proteases and accumulates in cytoplasmic vesicles of diseased individuals. It has been proposed that PrPsc when introduced into a normal cell causes the conversion of PrPc into PrPsc. The process is unknown but it could involve a chemical or conformational modification.

Several lines of evidence support the protein only model of infection.

  1. Nucleic acid is not necessary for infectivity
  2. PrPsc is associated with scrapie infectivity
  3. Susceptibility of a host to prion infection is co-determined by the prion inoculum and the PrP gene.
  4. Mutated genes can cause susceptibility to disease without apparent infection
  5. Crucial experiment

Evidence against the prion model
The existence of many different strains of scrapie, at least 15 whose latency, lesion patterns differ, can be propagated in the same inbred mouse strain. These can transmit serially without changes in properties in the same mouse strain homozygous for a single PrP genotype. One cannot argue that there is a distinct PrPc that is converted to distinct PrPsc for each strain. It must mean that a common PrPc is corrupted in a different way which seems improbable but there is now experimental support for it.

Are prion diseases genetic disorders?
Is the genotype of an animal or human the direct cause of a prion disease or a susceptibility factor? It has long been known that some genotypes of sheep often develop scrapie. In the UK the genotypes Ala136Ala, Arg154Arg, Gln171Gln, Val136Val, Arg154Arg and Gln171Gln are almost always identified in scrapie infected sheep. In contrast only one sheep with Ala136Ala, Arg154Arg and Arg171Arg has been identified with scrapie, these animals are resistant to both a scrapie and BSE challenge. If the genetic explanation is correct these scrapie-susceptible genotypes are common in Australia and New Zealand which are thought to be free of scrapie. Antipodean sheep have also been brought back to the UK and maintained in quarantine conditions and not developed scrapie. In other words the genotype does not confer scrapie on the animal but susceptibility to scrapie infection. Scrapie would appear to be an infectious disease not a genetic one. This observation may have implications for families carrying a mutant prion gene.

How can a protein be infectious?
PrPsc is a protease resistant form of PrPc, both are extensively post translationally modified. No chemical differences between the two forms of the protein have been detected. Clearly there must be some difference. One great problem is that infectivity ratio is about 100,000:1 so an infectious agent even if derived from PrPc may not be PrPsc and it could be chemically modified.

However, a more likely possibility is that the difference between PrPc and PrPsc is conformational. The 3D structure of part of the murine PrPc expressed in Escherichia coli has recently been determined. As expected from spectroscopy measurements PrPc is predominantly alpha helical and contains almost no beta sheet. The structure of PrPsc has not yet been determined but is predicted to be predominantly B sheet. It is proposed therefore that this protein can adopt 2 quite different stable conformations. The safe PrPc form is normally adopted but rarely it can switch to the PrPsc form. Mutations favour this switch. The proposal is that PrPsc is trans-dominant and converts PrPc to PrPsc in an exponential fashion. Precedents for this model do exist. There is a yeast mutant phenotype which does not correlate to any mutational difference in the gene structure but does correlate to a different protein structure. When normal protein is incubated with mutant protein its conformation is altered to the mutant form.

Strain Typing
The existence of multiple strains of prion agents by definition means that the agents carry strain specific information. The virino hypothesis states that this is a small nucleic acid molecule. The prion hypothesis states that it is due to differences in the chemical or tertiary structure of the prion protein. Strain discrimination relies on the use of mice of defined genotype and having different PrP gene sequences. Measurement of parameters such as incubation period in these mice and the pathological changes occurring in the brain are made.

Measurement of Incubation period
Precise quantities of brain homogenates from clinically affected animals are injected intra-cerebrally into mice. Animals are then assessed regularly for the definite appearance of disease using a defined set of observations. This measurement is very precise with errors of less than 2% of the mean.

Pathological changes
Strains show very different and reproducible differences in the pattern of vacuolar degeneration of different inbred mice. These effects are scored in a variety of different brain sections. Up to 12 topologically specific sites of the brain are scored for vacuolation, cortex, cerebellum, brain stem etc. This semi-quantitative assessment or lesion profile is then plotted. Individual strains have a characteristic and highly reproducible lesion profile in a given mouse genotype. Using this technique it is very clear that the recent outbreaks of new TSE diseases in various animals is caused by a prion with very similar characteristics, BSE, and quite distinct from previously recognized scrapie prion strains. Strain typing has also demonstrated beyond reasonable doubt that CJD are caused by a strain very much like the BSE agent. Some people now call this disease Human BSE.

Many people have been concerned since the recognition of the BSE epidemic in 1987 that it may pose a risk to humans. Strain typing studies show one major strain. BSE can transmit to many species experimentally e.g. sheep, pigs and macaque monkeys. Strain typing studies have confirmed that domestic cats, big cats and exotic ungulates have been infected by eating tainted beef. About 2 years ago a new variant of CJD was recognized in the British population. At the time of writing 39 cases have been confirmed. People have developed this form of CJD at strikingly early ages of 17-55. The neuropathology and early clinical symptoms are also very distinct from classical CJD. The CJD Surveillance Unit at Edinburgh and the committee charged with giving the government recommendations to deal with the threat to human health, SEAC, Spongiform Encepahalopathy Advisory Committee, concluded that the most likely cause is ingestion of infected beef. Strain typing studies of NV-CJD as described above have confirmed that this is very probably the case.

Earlier experiments involving the production of a protease fingerprint of PrPsc showed that 10 or so of the NV-CJD cases so far analysed had a unique form and distribution characteristic of a BSE infection and completely different to classical CJD. It seems therefore that BSE has infected humans by oral ingestion. An epidemic? It is currently unclear whether the incidence of NV-CJD will remain very low or become very high. Numbers are too low but there was a 50% increase in death rates last year. Clearly more can be expected. It will be interesting to watch the number of referrals to the CJD surveillance Unit. It is likely that a large proportion of the UK population has been exposed to the infectious agent. The size of the epidemic will depend on infectious dose exposure via the gastric route which may be cumulative.

Infection and Pathogenesis
Ingested prions may be absorbed across the gut wall at Peyers patches. These are a part of the MALT or mucosal associated lymphoid tissue. It is thought that the MALT presents microorganisms to the immune system in a contained and ideal fashion facilitating a protective immune response. Prions could be taken up in the same way. Lymphoid cells then phagocytose the particle and travel to other lymphoid sites such as nodes, the spleen and tonsils. The prion can replicate at these sites. Many of these sites are innervated and eventually the prion gains access to a nerve and then propagates back up the axon to the spinal cord and eventually the brain.

This indicates another compartment, in addition to the brain and the LRS, must express PrP if a peripheral prion challenge is to be successful. That compartment is probably a nerve. Mature B lymphocytes are also now known to be required for the development of the disease following infection from a peripheral route.

PrP over-expression facilitates the development of prion diseases. It may therefore follow that agents which reduce PrP expression will delay the onset of prion diseases. One can speculate that chemicals which bind to and stabilize the PrPc conformation may be beneficial. Similarly agents destabilizing the PrPsc conformation may be effective. Agents which interfere with the putative PrPc-PrPsc interaction might similarly be effective. A number of reagents showing affinity for amyloid proteins are known, congo red is an example. As knowledge of the structure of PrP increases, the chances of rationally deducing effective therapeutics based on these ideas increases. Finally, PrP expression is required for pathology. Chemicals affecting the endocytosis, exocytosis, intracellular trafficking and degradation of proteins and in particular PrP may also be effective. Amphotericin for instance is reported to delay prion disease in hamsters, although it apparently has little effect in humans.

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For further information
Phone: (250) 387-9513
Fax: (250) 356-8298
Email: Dr. Patrick Warrington

This page was last updated December 4, 2001