A pathogen, (from Greek πάθος pathos "suffering, passion", and γἰγνομαι (γεν-) gignomai (gen-) "I give birth to") an infectious agent, or more commonly germ is a biological agent that causes disease to its host. There are several substrates and pathways whereby pathogens can invade a host; the principal pathways have different episodic time frames, but soil contamination has the longest or most persistent potential for harboring a pathogen.
The body contains many natural orders of defense against some of the common pathogens (such as Pneumocystis) in the form of the human immune system and by some "helpful" bacteria present in the human body's normal flora. However, if the immune system or "good" bacteria is damaged in any way (such as by chemotherapy, human immunodeficiency virus (HIV), or antibiotics being taken to kill other pathogens), pathogenic bacteria that were being held at bay can proliferate and cause harm to the host. Such cases are called opportunistic infection.
Some pathogens (such as the bacterium Yersinia pestis, which may have caused the Black Plague, the Variola virus, and the Malaria protozoa) have been responsible for massive numbers of casualties and have had numerous effects on afflicted groups. Of particular note in modern times is HIV, which is known to have infected several million humans globally, along with the Influenza virus. Today, while many medical advances have been made to safeguard against infection by pathogens, through the use of vaccination, antibiotics, and fungicide, pathogens continue to threaten human life. Social advances such as food safety, hygiene, and water treatment have reduced the threat from some pathogens. Not all pathogens are negative. In entomology, pathogens are one of the "Three P's" (predators, pathogens, and parasitoids) that serve as natural or introduced biological controls to suppress arthropod pest populations.
Below is a list of different types of notable pathogens as categorized by their structural characteristics, and some of their known and predicted effects on infected host (person).
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Pathogenic viruses are mainly those of the families of: Adenoviridae, Picornaviridae, Herpesviridae, Hepadnaviridae, Flaviviridae, Retroviridae, Orthomyxoviridae, Paramyxoviridae, Papovaviridae, Polyomavirus, Rhabdoviridae, Togaviridae. Some notable pathogenic viruses cause: smallpox, influenza, mumps, measles, chickenpox, ebola, and rubella. Viruses typically range between 20-300 nanometers in length.
Although the vast majority of bacteria are harmless or beneficial, a few pathogenic bacteria can cause infectious diseases. The most common bacterial disease is tuberculosis, caused by the bacterium Mycobacterium tuberculosis, which affects about 2 million people mostly in sub-Saharan Africa. Pathogenic bacteria contribute to other globally important diseases, such as pneumonia, which can be caused by bacteria such as Streptococcus and Pseudomonas, and foodborne illnesses, which can be caused by bacteria such as Shigella, Campylobacter and Salmonella. Pathogenic bacteria also cause infections such as tetanus, typhoid fever, diphtheria, syphilis and Hansen's disease. Bacteria can often be killed by antibiotics. They typically range between 1-5 micrometers in length.
Fungi comprise a eukaryotic kingdom of microbes that are usually saprophytes but can cause diseases in humans, animals and plants. Fungi are the most common cause of diseases in crops and other plants. Life threatening fungal infections in humans most often occur in immunocompromised patients or vulnerable people with a weakened immune system, although fungi are common problems in the immunocompetent population as the causative agents of skin, nail or yeast infections. Most antibiotics that function on bacterial pathogens cannot be used to treat fungal infections due to the fact that fungi and their hosts both have eukaryotic cells. Most clinical fungicides belong to the azole group. The typical fungal spore size is 1-40 micrometer in length.
Prions are infectious pathogens that do not contain nucleic acids. Prions are abnormal proteins whose presence causes some Diseases such as scrapie, bovine spongiform encephalopathy (mad cow disease) and Creutzfeldt–Jakob disease.
One hypothesis regarding pathogens states that the longer a pathogen can survive outside of the body, the more dangerous it can be to a potential host. For example, the smallpox virus (variola virus) can survive outside the human body for approximately 885 days. It is also one of the most deadly pathogenic viruses, as it kills between 20-50% of the people it infects. The tuberculosis bacterium kills 1 in 5 of the people it infects, but only survives 244 days outside of its host. However, research into the basis of the ability of pathogens to cause disease provides evidence from multiple and diverse species of the existence of pathogenicity or virulence factors, encoded within the pathogens' genetic material, that facilitate microbes to cause disease.
In countries that have higher sanitation standards, pathogens cannot survive for as long outside of the human. This is seen as encouragement to mutations to the pathogen which would make it less deadly, as such mutations would allow the pathogen to survive in the host for longer periods of time.
One of the primary pathways by which food or water become contaminated is from the release of untreated sewage into a drinking water supply or onto cropland, with the result that people who eat or drink contaminated sources become infected. In developing countries most sewage is discharged into the environment or on cropland; even in developed countries there are periodic system failures resulting in a sanitary sewer overflow.
AIDS / HIV
Chronic Fatigue Syndrome
Pelvic Inflam. Dis.
Swine Flu Symptoms
West Nile Virus
Viral Skin Infection
Staphylococci, including Toxic Shock Syndrome (TSS):
The main pathogenic species is Staphylococcus aureus (aure = gold, golden), which causes most hospital-acquired infections. Multiple-drug-resistant strains have become such a problem due to overuse of antibiotics, that medical workers now refer to this by the nickname “M-D-R-S-A.” In 1999, following botched out-patient surgery on my stepfather, he was put on a ventilator which was contaminated and introduced a massive M-D-R-S-A infection into his lungs. He died after a couple months in ICU. In 2000, in the last couple months of my father-in-law’s life, nursing home staff battled M-D-R-S-A in bedsores on his heels, acquired during an immediately-previous hospitalization. These two incidents occurred in different hospitals in different cities.
Also, keeping your skin too “clean” can wash away the natural “antibiotics” in skin oils, actually making you more susceptible to bacterial infections.
Not all streptococci are bad: many are beneficial. Streptococcus thermophilus (thermo = heat; philia = brotherly love) is one of the bacteria that help turn milk into yogurt. Streptococcus pyogenes causes strep throat (pyo = pus, inflammation; gen = bear, produce).
This is a diplococcus (pneumo = lungs) which infects the lungs, causing <b>pneumonia</b>, and is spread by coughing.
Penicillin is effective for most of these, except where overuse has caused resistant strains. This is especially a problem with S. aureus in hospitals.
(gono = seed, generation, offspring; rrhea = flow, current) This disease is a sexually-transmitted disease (STD), and is caused by a bacterium of this type. One symptom is a pussy discharge from the genital area.
(meninges, meninx = a membrane [around the brain]; -itis = inflammation) This is an infection of the membranes covering the brain and/or spinal cord, and is life-threatening because of proximity of these membranes to the brain/spine.
(-ella = small) This disease is named after a Dr. Salmon who discovered it, and causes a type of food poisoning which has been in the news recently when it has made people sick after eating eggs, hamburger, etc. which contained it. Egg shells are porous — in a developing egg, that’s how the unhatched chick gets the air it needs to grow. Thus, washing eggs can actually cause Salmonella to penetrate the egg shell. If eggs are washed just before use, this is not a problem because the number of bacteria are usually negligible. However, if eggs are washed just after the hen lays them, then packaged into egg cartons at the egg factory, where they sit for a while until shipped to a grocery store, then sit for a while at the grocery store until purchased, then sit for a while in your refrigerator until used, that will give any Salmonella that did enter the egg a chance to grow and multiply, so by the time the eggs are used, the bacterial count is significantly higher, perhaps enough to make you sick. To prevent bacterial growth in eggs, if washing is even needed, they should not be washed until just before use.
This is a normal part of our intestinal flora, and is non-pathogenic if living in its normal environment in someone’s large intestine. However, if it gets elsewhere in the body, like the upper GI tract, it can make a person sick. This usually happens by the “fecal-oral route,” in other words, when someone drinks water or eats food washed in water containing untreated sewage. Restaurant iced tea is a notorious source of coliform bacteria. Our lab students have done studies which have shown that the tap water supplies at local restaurants are OK; homemade, freshly-brewed tea is OK; and freshly-brewed, restaurant iced tea is OK, but restaurant iced tea that has been sitting at room temperature for any length of time (as well as a sample of home-brewed tea that was added to a “dirty” pitcher) can have as many as millions of coliform bacteria per 100 mL of tea. In talking with students who work at some of these establishments, a repeating picture begins to emerge. In most cases, the tea is stored at room temperature in large, plastic-lined urns. Whenever the supply in an urn is getting low, the typical procedure is to make more tea and add this new, lukewarm tea to what is already there. In places that are open on a 24-hr basis, this goes on continually. In places that close for a few hours each night, any remaining tea is drained into a plastic pitcher, placed in the refrigerator overnight, then poured back into the urn (which, at most received a cursory rinse the night before) in the morning. Seldomly are the storage urns thoroughly cleaned and sterilized, and students have reported that when they have had to clean one of these urns, the insides are typically coated with slime (= bacterial growth). Typically the restaurants with the cleanest tea have taken the following steps:
· tea is stored in a stainless steel-lined container
· tea is quickly chilled after brewing and held at a cool temperature
· tea is made in smaller, more frequent batches
· the container used to store the tea is THOROUGHLY scrubbed clean and sterilized before EACH new batch of tea is added
· new tea is NEVER added to or mixed with “old” tea
· the urn is thoroughly sterilized at the end of each work day and left clean and dry overnight
· tea is not saved overnight for use the next day
· tea is not allowed to sit in the urns for more than a few hours before it is considered to be “expired”
Many other restaurants have “solved” this problem by switching to instant or other pre-packaged tea, thereby sacrificing flavor for convenience rather than taking the time to keep equipment clean. Consider that at home, most people typically make a pitcher of tea at a time, keep it refrigerated until use, then thoroughly wash the pitcher before adding a new batch of tea to it. If you want iced tea at a restaurant, order a cup of hot tea and a cup of ice, and make it yourself.
E. coli can also contaminate meat if the animal’s rectum is not carefully removed during the butchering process and fecal material comes into contact with the animal’s carcass. Food workers, anywhere, can spread E. coli if they do not thoroughly wash their hands after defecating/wiping.
Epidemics of this disease can be prevented by proper sewage handling. Cincinnati, as well as a number of other places, experienced a cholera epidemic in the 1800s. Consider that back then people didn’t know what we now know about bacteria, nor did most people have indoor plumbing. Often, when someone cared for someone else with cholera (changing clothes and bedding following an episode of diarrhea), the caregiver didn’t know to wash his/her hands afterward before eating. They just didn’t know that: nobody washed their hands as much as we do now, and without indoor running water, hand-washing was a lot more bother to do. Also, they didn’t have sewage treatment plants like we do, so typically this sewage was dumped on the ground or in a hole (the outhouse), or into the local water supply. Thus, ingestion of some of the bacteria either from one’s own hands or from drinking the water was a common source of exposure. One main symptom is diarrhea, and most victims die of dehydration. Now, people who do get cholera can recover if hospitalized so they can be given IV fluids to replace those lost by the diarrhea. Travelers to countries without modern sewage treatment facilities are often told to not drink water, eat locally-caught fish, and/or eat fresh vegetables washed in the local water to avoid the possibility of contracting cholera (among other diseases). Usually boiling the water and/or eating vegetables cooked in boiling water are often OK because the boiling kills the cholera bacteria.
When war forces people to flee from their homes to refugee camps, cholera is a major concern. Often, these refugee camps rapidly form on the bank of a lake or stream which is used as a source of drinking water for a large number of people under very crowded and primative conditions. There is neither time, money, nor materials to build a means of sanitary waste disposal, so the lake or river being used as a water supply quickly becomes contaminated. With few, if any, medical supplies available, the disease cannot be controlled and spreads rapidly.
(bubo = groin, swollen gland) This is also known as Black Death, and is infamous for wiping out about a third of the population of Europe in the Middle Ages (Imagine. . . out of a class of 30 students, what if 10 all died from the same disease?). Yersinia pestis, the bacterium which causes this disease, is found in wild rodents: rats, mice, squirrels, prairie dogs, and is transmitted by the bite of a flea from an infected animal or from another person by inhaling droplets from coughing. The incubation time is usually 2 to 5 days with abrupt onset. Symptoms include chills, fever, rapid pulse, and low blood pressure. The bacteria invade and multiply in lymph nodes, especially in the groin area. Enlarged lymph nodes, called buboes (bubo = groin, swollen gland) appear with or just after the fever, and the groin lymph nodes are most commonly affected (but others can also be infected). Infected lymph nodes are extremely swollen, tender, and firm; and usually, the overlying skin is reddened. The death rate in untreated victims is about 60%, usually from sepsis (a body-wide bacterial infection), in 3 to 5 days. If the person lives that long, the infected lymph nodes may fester and discharge pus in the second week. Another form of plague involves infection of the lungs instead. One main symptom of this form is coughing, with the sputum thus produced rapidly going from mucus to bloody. Most untreated patients with this form die within 48 hr of onset.
Medieval people made up a graphic little rhyme that is a reenactment (originally for/by adults) of plague that has survived to this day as a nursery rhyme. Some parents, knowing the history of this “game,” question the wisdom of teaching this to their children:
“Ring Around the Rosy” is about plague. The rosy red rings are the buboes. I’ve heard two possible explanations for the second line. One explanations suggests that the “Pocket full of posy” refers to the custom of wearing small bags of herbs (like onions or garlic) to prevent plague (which, obviously didn’t work so well). Another explanation suggests that this refers to the pus that forms in the pocket-like buboes. “Ashes, ashes, We all fall down” is a reference to the raging fever and the fact that most people died from the plague.
The story of the “Pied Piper of Hamelin” is also about plague. According to this old tale, the German town of Hamelin was overrun by plague-infested rats, which the piper led to their death in the river. The town council then double-crossed him and refused to pay him, so he secretly piped all the children away in the middle of the night and took them to Transylvania. To this day, there is an unexplained population of Germanic people in Transylvania, in the midst of all the Slovakians.
Two common pathogens in this genus cause botulism and tetanus (the disease). Botulism (botulus = sausage) is a type of food poisoning, and is often found in undercooked meats. The bacteria secrete toxins which are made of proteins which are resistant to digestion by our GI tract, so are absorbed through the intestinal wall, and are toxic to humans. Under adverse conditions, botulism bacteria (and other bacteria) can form spores, a dormant stage that is resistant to dry heat (roasting, broiling), but killed by moist heat (steaming, boiling, etc.). Also, typically microwaving does not provide enough heat for a long enough time to kill these bacteria. These bacteria grow well at body temperature and warm room temperature (summer temperature), thus it is important to beware of slowly-cooling soup with meat in it or left-over turkey stuffing (chill these quickly in the refrigerator, not sitting in the pot on the stove until they “cool”) and egg (especially raw) and/or meat-containing foods at picnics on hot day (deviled eggs containing mayonnaise are especially suspect, but any foods containing mayonnaise may be a problem). In general, vegetables, especially fresh/raw, are OK. Honey can contain small numbers of botulism spores which our bodies can effectively combat, so it’s generally not a concern. However, young babies’ immature immune systems have problems dealing with this small number of bacteria, thus infants under one year old should not be fed honey.
Tetanus (tetano = rigid, tense) is a disease in which all the person’s muscles stiffen and contract due to the presence of a toxin secreted by the bacteria. It’s not the rust on a rusty nail that’s the problem, it’s the possibility of tetanus bacteria living there. Note, by the way, that the term “tetanus” technically refers to the condition of all the muscles being stiffened and contracted, no matter what the cause. Injury of a body part and/or certain drugs (strychnine) can cause tetanus. In this case, the word “tetanus” is used to refer not only to the condition of the muscles, but also to the bacteria and their toxin which, in this case, is the cause of the condition.
(tuberculum = a little knob, swelling) This disease was at a low for a long time, but now is a problem again because of multiple-drug-resistant strains that have evolved due to the overuse of antibiotics. These bacteria live in the lungs and destroy lung tissue.
This is a disease, better known by another name, with an ancient history. It’s not very contagious, but ancient and Medieval people didn’t know that, so people with this disease were required to live outside of town and not associate with “normal” people, much the way some AIDS victims have been treated today. We now know that while this bacterium can’t be killed — the disease can be treated but never cured, and victims must take antibiotics “for ever” — a person on antibiotics can lead a normal life and is not contagious. However, because of the historical, unjustified fear of this disease, its name was changed to Hansen’s disease so victims could have a chance at a fairly normal life without discrimination. If you haven’t guessed from this description, the original name of this disease was leprosy. This affects the person’s nerves, so (s)he loses his/her sense of feeling in affected body parts, often resulting in a greater danger of injury to those body parts (imagine not being able to tell when something is too hot to touch, thus not instinctively pulling back your hand). Armadillos can carry the leprosy bacterium.
This bacterium is spread by intercourse (it is an STD). The initial symptom is a sore on the genitalia followed later by a serious, general infection. A baby can become blind if (s)he gets syphilis in his/her eyes as (s)he is being born, thus hospitals routinely squirt silver nitrate (AgNO3) in newborns’ eyes, whether their mothers have this infection or not, thereby causing the babies’ eyes to become irritated and puffy (If you have ever worked with this in chemistry lab, you may know that if you get it on your skin, and your skin is subsequently exposed to light, that area of skin will turn black until it wears off.).
This bacterium is spread by the bite of a deer tick, thus is more common around wooded, rural areas. It is named after the town of Lyme, Conn., where it was first observed. There may be some inflammation around the site of the bite, but not always. However, if untreated at that stage, the main symptom is an arthritis-like condition that can last for months.
Protists (pronounced /ˈproʊtɨst/) are a diverse group of eukaryotic microorganisms. Historically, protists were treated as the kingdom Protista, which includes mostly unicellular organisms that do not fit into the other kingdoms, but this group is contested in modern taxonomy.Instead, it is "better regarded as a loose grouping of 30 or 40 disparate phyla with diverse combinations of trophic modes, mechanisms of motility, cell coverings and life cycles."
The protists do not have much in common besides a relatively simple organization—either they are unicellular, or they are multicellular without specialized tissues. This simple cellular organization distinguishes the protists from other eukaryotes, such as fungi, animals and plants.
The term protista was first used by Ernst Haeckel in 1866. Protists were traditionally subdivided into several groups based on similarities to the "higher" kingdoms: the one-celled animal-like protozoa, the plant-like protophyta (mostly one-celled algae), and the fungus-like slime molds and water molds. Because these groups often overlap, they have been replaced by phylogenetic-based classifications. However, they are still useful as informal names for describing the morphology and ecology of protists.
Protists live in almost any environment that contains liquid water. Many protists, such as the algae, are photosynthetic and are vital primary producers in ecosystems, particularly in the ocean as part of the plankton. Other protists, such as the Kinetoplastids and Apicomplexa, are responsible for a range of serious human diseases, such as malaria and sleeping sickness.
Some protists reproduce sexually (conjugation), while others reproduce asexually (binary fission).Some species, for example Plasmodium falciparum, have extremely complex life cycles that involve multiple forms of the organism, some of which reproduce sexually and others asexually. However, it is unclear how frequently sexual reproduction causes genetic exchange between different strains of Plasmodium in nature and most populations of parasitic protists may be clonal lines that rarely exchange genes with other members of their species.
Some protists are significant pathogens of both animals and plants. For example Plasmodium falciparum which causes malaria in humans and Phytophthora infestans which causes potato blight. A more thorough understanding of protist biology may allow these diseases to be treated more efficiently.
Parasitic worms or helminths (pronounced /ˈhɛlmɪnθs/) are a division of eukaryotic parasites that, unlike external parasites such as lice and fleas, live inside their host. They are worm-like organisms that live and feed off living hosts, receiving nourishment and protection while disrupting their hosts' nutrient absorption, causing weakness and disease. Those that live inside the digestive tract are called intestinal parasites. They can live inside humans as well as other animals. Approximately 3 billion people globally are infected with helminths.Helminthology is the study of parasitic worms and their effect on their hosts. The word helminth comes from Greek hélmins, a kind of worm.Parasitic worms are categorized into three groups: cestodes (tapeworms), nematodes (roundworms), and trematodes (flukes).
Parasitic worms are sequential hermaphrodites and reproduce depending on the species of worm, either with the presence of a male and female worm, joining sperm and eggs, producing fertile eggs, such as hookworms, or by breaking off segments that contain both male and female sex organs that are able to produce fertile eggs without the presence of a male or female (e.g., tapeworms).
All worm offspring are passed on through poorly-cooked meat, especially pork, wild fish, and beef, contaminated water, feces and mosquitoes. However, it is estimated that 40 million Americans are infected with the most common roundworm in the United States, the pinworm.
Worm eggs or larvae or even adults enter the human body through the mouth, anus, nose, or skin, with most species attaching themselves to the intestinal tract. With the presence of digestive enzymes, worm egg shells are dissolved, releasing a brand-new worm; unlike its egg shell, the parasitic worm is protected from the body's powerful digestive enzymes by producing a protective keratin layer.
In patients with a heavy worm load, parasite infection is frequently symptomatic. Conditions associated with intestinal helminth infection include intestinal obstruction, insomnia, vomiting, weakness, and stomach pains while the natural movement of worms and their attachment to the intestine may be generally uncomfortable for their hosts.The migration of Ascaris larvae through the respiratory passageways can also lead to temporary asthma and other respiratory symptoms. These side effects may all act to distract students in an academic setting and reduce their clarity of mind and intellectual productivity.
In addition to the low-level costs of chronic infection, helminth infection may be punctuated by the need for more serious, urgent care; for example, the World Health Organization found that worm infection is common reason for seeking medical help in a variety of countries, with up to 4.9% of hospital admissions in some areas resulting from the complications of intestinal worm infections and as many as 3% of hospitalizations attributable to ascariasis alone.
Also worth considering is the fact that the immune response triggered by helminth infection may drain the body’s ability to fight other diseases, making affected individuals more prone to co-infection. There are reasonable evidences indicating that helminthiasis is responsible for the unrelenting prevalence of AIDS and tuberculosis in developing, particularly African, countries. A review of several data clearly revealed that effective treatment of helminth infection reduces HIV progression and viral load, obviously by improving helminth-induced immune suppression.
Once the links between helminth infection and various forms of malnutrition are established, there are a number of pathways by which parasite burden may affect cognition. For example, poor performance on normal growth indicators appears to be correlated with lower school achievement and enrollment, worse results on some forms of testing, and a decreased ability to focus; on the other hand, iron deficiency may result in “mild growth retardation,” difficulty with abstract cognitive tasks, and “lower scores...on tests of mental and motor development...[as well as] increased fearfulness, inattentiveness, and decreased social responsiveness” among very young children. Anemia has also been associated with reduced stamina for physical labor, a decline in the ability to learn new information, and “apathy, irritability, and fatigue.”
These connections are supported by a number of deworming studies. For example, using 47 students from the Democratic Republic of the Congo, Boivin and Giardani (1993) found that iron supplements acted as a complement to deworming medication, producing better effects on mental cognition when they were applied in conjunction than when they were individually administered. He hypothesized that this result was due to the fact that iron supplements may “improve [students’] physical well-being to the point of enhancing attentional or arousal mechanisms influential in learning and cognitive performance,” with deworming medication only acting to extend these benefits by further reducing the tendency to anemia.
Perhaps even more fascinating are a number of papers that take the study of intestinal helminth beyond the malnutrition-cognition link to focus on the connections between worm infections and memory formation. For example, Nokes et. al. (1992) find that interventions to reduce whipworm infection in 159 Jamaican schoolchildren led to better “auditory short-term memory” and “scanning and retrieval of long-term memory;” particularly fascinating was his discovery that a nine-week period was all that was necessary for dewormed students to “catch up” to their worm-free peers in test performance.Nokes’ optimistic conclusion that “whipworm infection[‘s]...adverse effect on certain cognitive functions...is reversible by therapy” is particularly significant because it suggests that the effects of worms on intellectual performance may not be restricted to the mechanism of long-term malnutrition, since the physical and developmental effects of such malnutrition would theoretically be irreversible.
Also worth noting are the studies of Ezeamama et. al. (2005) and Sakti et. al. (1999), which studied worm burden in the Philippines and Indonesia, respectively. Both authors found significant negative impacts of helminthic infection on memory and fluency, findings that are particularly meaningful because they included controls for socioeconomic status, hemoglobin levels, and proxies of nutrition (nutritional status and stunting, respectively). As Ezeamama observes, these studies suggest “that undernutrition is not the primary mediator of the observed relationships”between worm infection and intellectual performance, particularly because their findings were significant in aspects of intellect that went beyond mere cognition and reaction time.
Finally, Watkins and Pollitt observe that, much as physical activity is “nutritionally mediated” as patients with heavy worm burden struggle to preserve energy and fight malnutrition, so too could “the poorly nourished mind similarly adapt...by reducing mental effort in the form of arousal and sustained attention.” While they find little evidence that this adaptation would provide benefits in the form of energy conservation, it is clear that the active course of ongoing parasitic disease could impose other, more direct limitations on an individual’s attention span.
A proteinaceous infectious particle, or prion, (pronounced /ˈpriː.ɒn/ ) is an infectious agent composed primarily of protein.The word prion, coined in 1982 by Dr. Stanley B. Prusiner, is a portmanteau derived from the words protein and infection.Prions are the cause of a number of diseases in a variety of mammals, including bovine spongiform encephalopathy (BSE, also known as "mad cow disease") in cattle and Creutzfeldt–Jakob disease (CJD) in humans. In general usage, prion refers to the theoretical unit of infection. All known prion diseases affect the structure of the brain or other neural tissue and all are currently untreatable and universally fatal.
Prions propagate by transmitting a mis-folded protein state: so as with viruses the protein cannot replicate by itself. Instead, when a prion enters a healthy organism the prion form of a protein induces pre-existing normal forms of the protein to convert into the rogue form. Since the new prions can then go on to convert more proteins themselves, this triggers a chain reaction that produces large amounts of the prion form All known prions induce the formation of an amyloid fold, in which the protein polymerises into an aggregate consisting of tightly packed beta sheets. Amyloid aggregates are fibrils, growing at their ends, and replicating when breakage causes two growing ends to become four growing ends. The incubation period of prion diseases is determined by the exponential growth rate associated with prion replication, which is a balance between the linear growth and the breakage of aggregates.
This altered structure is extremely stable and accumulates in infected tissue, causing tissue damage and cell death.This structural stability means that prions are resistant to denaturation by chemical and physical agents, making disposal and containment of these particles difficult. Prions come in different strains, each with a slightly different structure, and most of the time, strains breed true. Prion replication is nevertheless subject to occasional epimutation and then natural selection just like other forms of replication. However, the number of possible distinct prion strains is likely far smaller than the number of possible DNA sequences, so evolution takes place within a limited space.
In scientific notation, PrPC refers to the endogenous form of prion protein (PrP), which is found in a multitude of tissues, while PrPSc refers to the misfolded form of PrP, that is responsible for the formation of amyloid plaquesand neurodegeneration. The precise structure of the prion is not known, though they can be formed by combining PrPC, polyadenylic acid, and lipids. Proteins showing prion-type behavior are also found in some fungi, which has been useful in helping to understand mammalian prions. Fungal prions, however, do not appear to cause disease in their hosts and may even confer an evolutionary advantage through a form of protein-based inheritance.
It has been recognized that prion diseases can arise in three different ways: acquired, familial, or sporadic. It is often assumed that the diseased form directly interacts with the normal form to make it rearrange its structure. One idea, the "Protein X" hypothesis, is that an as-yet unidentified cellular protein (Protein X) enables the conversion of PrPC to PrPSc by bringing a molecule of each of the two together into a complex.
Current research suggests that the primary method of infection in animals is through ingestion. It is thought that prions may be deposited in the environment through the remains of dead animals and via urine, saliva, and other body fluids. They may then linger in the soil by binding to clay and other minerals.
Prions cause neurodegenerative disease by aggregating extracellularly within the central nervous system to form plaques known as amyloid, which disrupt the normal tissue structure. This disruption is characterized by "holes" in the tissue with resultant spongy architecture due to the vacuole formation in the neurons.Other histological changes include astrogliosis and the absence of an inflammatory reaction. While the incubation period for prion diseases is generally quite long, once symptoms appear the disease progresses rapidly, leading to brain damage and death. Neurodegenerative symptoms can include convulsions, dementia, ataxia (balance and coordination dysfunction), and behavioural or personality changes.
All known prion diseases, collectively called transmissible spongiform encephalopathies (TSEs), are untreatable and fatal. A vaccine has been developed in mice, however, that may provide insight into providing a vaccine in humans to resist prion infections. Additionally, in 2006 scientists announced that they had genetically engineered cattle lacking a necessary gene for prion production – thus theoretically making them immune to BSE, building on research indicating that mice lacking normally occurring prion protein are resistant to infection by scrapie prion protein.
Many different mammalian species can be affected by prion diseases, as the prion protein (PrP) is very similar in all mammals. Due to small differences in PrP between different species it is unusual for a prion disease to be transmitted from one species to another. The human prion disease variant Creutzfeldt-Jakob disease, however, is believed to be caused by a prion which typically infects cattle, causing Bovine spongiform encephalopathy and is transmitted through infected meat.
Infectious particles possessing nucleic acid are dependent upon it to direct their continued replication. Prions, however, are infectious by their effect on normal versions of the protein. Sterilizing prions therefore involves the denaturation of the protein to a state where the molecule is no longer able to induce the abnormal folding of normal proteins. Prions are generally quite resistant to proteases, heat, radiation, and formalin treatments, although their infectivity can be reduced by such treatments. Effective prion decontamination relies upon protein hydrolysis or reduction or destruction of protein tertiary structure. Examples include bleach, caustic soda, and strong acidic detergents such as LpH.134°C (274°F) for 18 minutes in a pressurized steam autoclave may not be enough to deactivate the agent of disease.Ozone sterilization is currently being studied as a potential method for prion denature and deactivation.Renaturation of a completely denatured prion to infectious status has not yet been achieved, however partially denatured prions can be renatured to an infective status under certain artificial conditions.
The World Health Organization recommends any of the following three procedures for the sterilization of all heat-resistant surgical instruments to ensure that they are not contaminated with prions:
Pathogenic fungi are fungi that cause disease in humans or other organisms. The study of pathogenic fungi is referred to as medical mycology. Although fungi are eukaryotic organisms many pathogenic fungi are also microorganisms.
Candida species are important human pathogens that are best known for causing opportunist infections in immunocompromised hosts (e.g. transplant patients, AIDS sufferers, cancer patients). Infections are difficult to treat and can be very serious: 30-40% of systemic infections result in death. The sequencing of the genome of C. albicans and those of several other medically-relevant Candida species has provided a major impetus for Candida comparative and functional genomic analyses. These studies are aiding the development of sensitive diagnostic strategies and novel antifungal therapies.
Aerosolized Aspergillus spores are found nearly everywhere so we are routinely and almost constantly exposed to them. Such exposure is a normal part of the human condition and generally poses no adverse health effects. Nevertheless, Aspergillus can and does cause disease in three major ways: through the production of mycotoxins; through induction of allergenic responses; and through localized or systemic infections. With the latter two categories, the immune status of the host is pivotal. Allergies and asthma are thought to be caused by an active host immune response against the presence of fungal spores or hyphae. In contrast, with invasive aspergillosis, the immune system has collapsed and little or no defence can be mounted.
The most common pathogenic species are Aspergillus fumigatus and Aspergillus flavus. Aspergillus flavus produces aflatoxin which is both a toxin and a carcinogen and which can potentially contaminate foods such as nuts. Aspergillus fumigatus and Aspergillus clavatus can cause allergic disease. Some Aspergillus species cause disease on grain crops, especially maize, and synthesize mycotoxins including aflatoxin. Aspergillosis is the group of diseases caused by Aspergillus. The symptoms include fever, cough, chest pain or breathlessness. Usually, only patients with weakened immune systems or with other lung conditions are susceptible.
Cryptococcus neoformans can cause a severe form of meningitis and meningo-encephalitis in patients with HIV infection and AIDS. The majority of Cryptococcus species live in the soil and do not cause disease in humans. Cryptococcus neoformans is the major human and animal pathogen. Cryptococcus laurentii and Cryptococcus albidus have been known to occasionally cause moderate-to-severe disease in human patients with compromised immunity. Cryptococcus gattii is endemic to tropical parts of the continent of Africa and Australia and can cause disease in non-immunocompromised people.
Histoplasma capsulatum can cause histoplasmosis in humans, dogs and cats. The fungus is most prevalent in the Americas, India and southeastern Asia. It is endemic in certain areas of the United States. Infection is usually due to inhaling contaminated air.
Stachybotrys chartarum or "black mold" can cause respiratory damage and severe headaches. It frequently occurs in houses in regions that are chronically damp.
Treatment with antifungal drugs often results in the appearance of resistant strains of fungi. Various mechanisms leading to resistance have been described. For example, a number of resistant clinical isolates overexpress genes encoding drug efflux pumps. Recent advances in molecular biology have allowed the study of the phenomenon of multi-drug resistance on a genome-wide scale. DNA microarrays are being used to study the expression profiling of pathogenic fungi and proteomics is aiding research in the development of resistance to various antifungal drugs.