VALDOSTA STATE UNIVERSITY

Biology 2900--Spring 2005

1. In honor of Jenner, Snow, Pasteur, and Koch
1. smallpox -- once one of the major diseases accounting for miillions of deaths and possibly influencing world history; now, thanks to a global eradication program nearly eliminated from existence (last naturally occuring case in Somalia in 1977); usually cited as one of the major threats for bioterrorism
1. symptoms -- the first symptoms,1 to 2 weeks after exposure, include high fever, malaise, head and body aches, and sometimes vomiting; rash develops, initially in the mouth, but usually speading over the body within 24 hours; the rash develops into raised bumps which fill with opaque fluid, often a central depression; the rash develop into hard pustules (feel like BB's under the skin); pustules scab over; scabs eventually fall off, leaving scars; individual is contagious until the last scab falls off, most contagious during the oral stage; 30% mortality
   
2. causative agent -- Variola virus, an enveloped double-stranded DNA virus in the orthopoxvirus family
3. pathogenesis -- enters through respiratory mucosa, moves to lymph nodes where they multiply; eventually reach small capillaries near the epidermis; enter epidermal cells, activity leads (somehow) to the characteristic rash
   
4. prevention -- initially through variolation (deliberate inoculation with smallpox virus); Jenner credited with vaccination using the related, but relatively harmless, cowpox; currently vaccination not recommended except for some health care workers and military personnel; vaccination is with live vaccinia virus
   
2. rabies -- nervous system disorder first  described by Democritus in the fifth century BC, endemic in many mammal populations (dogs, racoons, bats, coyotes, skunks, etc.); usually fatal for humans once symptoms develop (6 known survivors)
1. symptoms -- begins with common symptoms of viral infection: fever, head and muscle aches, sore throat, fatigue and nausea; may be tingling at the site of infection (symptoms begin 13 days to a year (usually 1 to 2 months) after entry of the virus); progress to encephalitis, agitation, confusion, hallucinations, seizures, hypersensitivity to light, touch and sound, increased temperature, difficulty swallowing, hydrophobia, coma; death is usually only days after the first appearance of symptoms
2. causative agent -- rabiesvirus, a member of the rhabdoviridae (enveloped, with single-stranded negative-sense RNA)
3. pathogenesis -- transmission through the saliva of an infected animal (or bat feces), either as the result of a bite or the inhalation of an aerosol; multiplies initially in muscle cells, moves to the axons of neurons and eventually, through neurons to the brain (long incubation period); multiplies in brain tissue, forming Negri bodies (characteristic of rabies and the basis for rabies tests); travels through additional neurons to other parts of the body, where the virus infects other organs, including salivary glands
4. epidemiology -- usually from bites of infected animals, in the United States mostly from wild-life; asymptomatic cases have led to organ transplants as a mode of infection
5. prevention and treatment -- extensive programs for vaccinating dogs and wild-life are in place in most developed countries (a few European countries are rabies-free); not all bites by rabid animals lead to rabies, but the odds are greatly improved by vaccination soon after the bite (Pasteur); immunoglobulin injections also help
3. epidemic cholera -- implicated in 7 pandemics since the early 1800's (the last in 1961); 200,000 deaths in the United States alone between 1832 and 1836; localized outbreaks a concern whenever sanitation breaks down because of natural disasters or war (refugee camps); sporadic cases occur in the United States, especially along the Gulf coast
1. symptoms -- severe watery diarrhea (maybe 20 liters per day--rice water stool), vomiting (early stages), muscle cramps from dehydration and electrolyte imbalances
2. causative agent -- Vibrio cholerae, a curved Gram-negative rod capable of surviving alkaline conditions and high salt concentrations; common in coastal waters around the world (most strains not pathogenic); pathogenic strains apparently contain a filamentous (lysogenic) bacteriophage, which contains the gene that codes for the toxin
3. pathogenesis -- infection/transmission commonly through the fecal to oral route--large numbers of bacteria needed because of the acid conditions in the stomach; attach to cells lining the small intestine and secrete an A-B type exotoxin (B-part binds the toxin to a cellular receptor, A-part causes the physiological change in the host); toxin leads to the production of cAMP which leads to activation of chloride ion pumps in the host cell's membrane; ions are pumped out of the cell into the intestinal lumen, water and other electrolytes follow
4. epidemiology -- infections typically from drinking contaminated water, foods contaminated with feces and some crabs
5. prevention and treatment -- good sanitation, thoroughly cooked foods, fresh produce only if peeled by the consumer if traveling in cholera-prone regions; vaccines available; treat the symptoms (rehydration, electrolytes), prompt treatment reduces the mortality to less than 1% (25 to 50% if untreated); antibiotics reduce severity
2. Some intestinal diseases
1. Shigellosis -- at least 14,000 cases per year in the United States, possibly as many as 400,000; this is a reportable disease
1. symptoms -- diarrhea (sometimes bloody), fever, abdominal cramps starting about 2 days after exposure; usually ends after a week; fever may be high enough to cause convulsions in the very young; some versions have a 5-15% mortality rate; shigellosis rarely (3% of diagnosed cases) leads to Reiter's syndrome (joint pain, eye irritation, painful urination) which might last for months
2. causative agent -- Shigella sonnei (2/3 of US cases), S. flexneri (1/3 of US cases), S. dysenteriae (causes deadly epidemics in developing countries, especially in Africa, very rare in the US); Gram negative rods related to E. coli
3. pathogenesis -- the bacteria are injested by phagocytes in gut-associated lymphoid tissue (mucosal-associated lymphoid tissue) in the large intestine; they survive and are released at the base of the epithelium; here they attach to epithelial cells and are again injested (attachment is mediated by genes on a large plasmid); in the epithelial cells they break out of the food vacuole (phagosome) and multiply in the cytoplasm; cause the actin component of the cytoskeleton to push them ito the next cell; host cell dies as the multitudes of bacteria thrive inside of them--patches of the intestine without epithelium, highly inflammed, pus-covered; strains of S. dysenteriae form Shiga toxin, an A-B toxin that blocks protein synthesis and leads eventually to hemolytic uremic syndrome (same toxin as that produced by E. coli strains that lead to hemolytic uremic syndrome.
4. epidemiology -- transfer via the fecal-to-oral route (bad sanitation, contaminated food, poor handwashing technique, day-care centers); note-worthy that as few as 10 cells can cause an infection (survive stomach acid)
5. prevention and treatment -- proper food handling, sanitation, hand-washing; ampicillin and cotrimoxazole commonly used for treatment, but 20% of strains now resistant; must have two clear stool samples taken 48 hours apart to be declared free and ready to return to day-care or food-handling job
2. Escherichia coli gastroenteritis -- E. coli is a common member of our intestinal flora, but can cause a number of intestinal problems all lumped together here as gastroenteritis of varying degrees of severity; severity depends to a large degree which strain is causing the problem
1. general symptoms -- vary from vomiting and loose bowels to profuse watery diarrhea to severe cramps and bloody diarrhea (dysentery); usually no fever with the toxigenic form; recovery usually within 10 days; hemolytic uremic syndrome may develop
2. specific agents, symptoms, pathogenesis
1. enterotoxigenic E. coli -- cause of many cases of traveler's and infant diarrhea; bacteria attach to the epithelium of the small intestine using special adhesins; secrete toxins, one version of which is very similar in structure and effect to cholera toxin
2. enteroinvasive E. coli --  invades the epithelium of the large intestine, causing localized cell death; results in fever, cramps, and blood and pus in feces; similar to shigellosis
   
3. enteropathogenic E. coli -- common in hospital nurseries and in bottle-fed babies in developing countries; special adhesins alter the form of epithelial cells in the small intestine; leads to fever, vomiting, watery diarrhea with mucus
4. enterohemorrhagic E. coli -- severe form of E. coli gasteroenteritis, usually associated with strain O157:H7; produce a group of toxins that poison the ability of epithelial cells in the large intestine to make protein, including toxins related to Shiga toxin; unlike shigellosis, bacterial cells do not invade the epithelium; leads to fever, abdominal cramps, bloody diarrhea without pus; 2-7% develop hemolytic uremia syndrome blood in the urine and kidney failure
3. general pathogenesis -- at least two of the virulence factors (adhesin,enterotoxin) are carried by plasmids so can be passed from bacterium to bacterium; many pathogenic strains have more than one virulence plasmid
4. epidemiology -- common in travelers; fecal to oral route via contaminated food, unpasteurized milk and juice, contaminated water
5. prevention and treatment -- hand-washing, pasteurization of drinks, thorough cooking of food; treat symptoms and treat with bismuth compounds and with antibiotics
3. Salmonellosis -- at least 40,000 per year in the US, maybe more than a million; about 600 die from severe cases, mostly the very young, the very old, and the immunocompromised
1. symptoms -- diarrhea, abdominal pain, nausea, vomiting, fever; may lead to septic arthritis and sepsis
2. causative agent -- any one of over 2000 strains of Salmonella, another genus of Gram-negative rods related to E. coli
3. pathogenesis -- needs a fairly large inoculum to pass through the stomach and infect the intestine; in the small intestine, they attach to the epithelium and trick the cell into injesting them; multiply in the food vacuole (phagosome); cells are discharged at base (exocytosis) where they are quickly killed by macrophages; symptoms are caused by an inflammation response
4. epidemiology -- transfer via the fecal-to-oral route; reptiles frequently discharge Salmonella in feces; eggs and poultry often contaminated; other meats and vegetables can also be sources of infection
5. prevention and treatment -- proper sanitation and hand-washing; proper cooking of eggs, poultry, meat; pet reptile sales have been curbed; antibiotics usually not required for recovery, but there are many Salmonella strains with multi-drug resistance
4. Typhoid fever -- Typhoid Mary; currently only 400 cases per year in the US, but an estimated 20 million elsewhere with 200,000 deaths
1. symptoms -- high fever, headache, malaise, muscle ache, constipation (no diarrhea), followed by confusion, delirium, intestinal perforation, and (sometimes) death; agent may take up permanent residence in the gall bladder
2. causative agent -- some strains of Salmonella (serotype Typhi)
3. pathogenesis -- similar to salmonellosis at first, but can survive injestion by macrophages and be carried throughout the body; when released from the macrophages they can take up residence in other tissues, causing prolonged fever, abscesses, septicemia, shock, destruction of lymphoid tissue in the small intestine with intestinal rupture
4. epidemiology -- transfer via the fecal-to-oral route; contaminated food and water; direct transmission from a carrier (still fecal-to-oral)
5. prevention and treatment -- proper hand-washing, food preparation, sanitation; can be treated with antibiotics, vaccine is available for travelers; in some cases carriers must have the gall bladder removed
5. Viral gastroenteritis (stomach flu) -- millions of cases in the US each year, thousands of cases reach the hospital; globally responsible for 100,000s of deaths
1. symptoms -- sudden onset of vomiting and slight fever followed by watery diarrhea, usually starting 12-48 hours after exposure; symptoms last anywhere from a day to a week, depending on the causative agent
2. causative agents -- numerous viruses from different groups, most notably rotavirus (double-walled capsid, double-stranded 11-segmented RNA, particle has a wheel-like appearance), Norwalk virus (norovirus--spherical capsid, single-stranded RNA); the more severe cases requiring hospitalization are usually associated with rotaviruses, noroviruses are more widespread
3. pathogenesis -- infect epithelium of the small intestine, leading to cell death and inflammation
4. epidemiology -- transmission through the fecal-oral route; norovirus can cause symptom with as few as 10 particles; both rotaviruses and noroviruses are relatively stable in the environment, norovirus is resistent to elevated temperature (steamed shellfish) and chlorine; suggestion that norovirus is present in seawater/seafood that does not have a history of fecal contamination
5. prevention and treatment -- proper sanitation, food-handling, disinfectant; vaccine available for rotavirus, but not recommended because of possible lethal side-effects (bowel obstruction); treat symptoms (rehydration)
3. In the news recently
1. polio -- once a common and devasting disease, with 21,000 serious cases per year in the US, up to 300,000 globally, now nearly gone -- endemic in India, Pakistan, Afghanistan, Niger, Nigeria, and Egypt (1212 cases this week) (in the news because of new efforts aimed completely eradicating it in the next few years (Gates foundation)
1. symptoms -- up to 95% of infections have no symptoms, but can still shed infectious agents; 4% - 8% give non-descript symptoms (upper respiratory tract infection (sore throat, fever), gastroenteritis (nausea, vomiting, constipation), flu-like symptoms; in 1% - 2% of cases progresses to the non-paralytic form--stiffness in neck back and legs; less than 1% of cases progress to the paralytic form--severe muscle-aches and spasms progressing to flaccid paralysis, leading to either complete recovery or some degree of permanent paralysis; does not affect sensory nerves; post-polio syndrome, occurs years later, muscle degeneration, apparently as neurons die
2. causative agent -- caused by types 1, 2, and 3 polioviruses; non-enveloped, ssRNA, positive sense
3. pathogenesis -- enters through the fecal to oral route; infects epithelium in throat and intestines; rarely spreads to bloodstream, and from there to motor nerves (cells must have proper surface protein to be infected); infected cells are killed, leading to symptoms; eventually eliminated by immune system
4. epidemiology -- humans are the only host/reservoir; transmission by the fecal to oral route (maybe oral to oral); infectious a week before symptomatic; highly communicable
5. prevention and treatment -- sanitation plus vaccination; initially two versions--Salk (inactivated, injected) and Sabin (active, attenuated, oral); now there are highly effective trivalent forms of each; US stopped using the oral version in 2000--many of the last cases of paralytic polio were attributed to the vaccine; in latest push to end polio, plans are to use a monovalent oral vaccine against Type 1 (more effective than the trivalent versions)

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