VALDOSTA STATE UNIVERSITY

Biology 2900--Spring 2005

1. Meningitis -- inflammation of the meninges; can be caused by a large number of bacteria and viruses, including Haemophilus influenzae and Streptococcus pneumoniae; we will concentrate on just a few
1. Meningococcal meningitis -- fast, dangerous, but treatable version; may  lead to epidemics
   
1. symptoms -- begin with a mild cold, then sudden throbbing headache, fever, neck and back stiffness, nausea, vomiting, periodic loss of consciousness, coma; purplish petechial spots characteristic; cloudy spinal fluid; death within 24 hours possible
2. causative agent -- Neisseria meningitidis, Gram-negative diplococci; multiple serotypes
   
3. pathogenesis -- cells inhaled, make their way to the blood through respiratory epithelium (or elsewhere), and from the blood to cerebrospinal fluid; reproduce rapidly in the rich medium (faster than phagocytes (neutrophils) can eat them), reducing glucose levels; pus formation and other aspects of the inflammation response increase pressure on nervous tissue; cells in the blood-stream release endotoxin so localized and general shock can result
4. epidemiology -- cells present in upto 15% of healthy individuals, usually in upper respiratory system where harmless; movement into meninges in individuals understandable; not quite clear why epidemics occur
5. prevention -- vaccine available to 4 major serotypes, not particularly effective, but recommended for those traveling to countries where epidemics are common, suggested for consideration by college students living in dorms; prophylactic antibiotics used more commonly to control outbreaks
6. treatment -- usually treated with rifampin, penicillin, etc.
2. Viral meningitis -- more common and generally milder than bacterial meningitis
1. symptoms -- sudden onset of fever, headache, stiff neck; sensitivity to light, nausea and vomiting also common; other symptoms, depending on the agent
2. causative agents -- many different viruses can be responsible; most are picornaviruses (coxsackievirus, echovirus); mumps virus was once a common cause
3. pathogenesis -- the picornaviruses general enter the blood through lymphoid tissue in the intestine; from there they move to the meninges, where they attack the cells of the meninges; inflammation response generally milder, fewer phagocytes (macrophages) enter, no drop in glucose
4. epidemiology -- the picornaviruses are common, enter via the fecal-to-oral route; mumps virus enters through the respiratory route
5. prevention and treatment -- general cleanliness; vaccine for mumps, but not the others; no treatment
3. Epidemic viral encephalitis --viral encephalitis is usually dangerous diseases with potential for permanent brain damage; many viruses can be responsible, including herpes simplex, mumps, etc.; cases are sporadic; epidemic encephalitis can infect lots of people in one area, again with many causes, mostly carried by arthropods
1. symptoms -- abrupt onset with fever, headache, vomiting, mental problems up to coma
2. causative agents -- usually one of the arboviruses (carried by arthropods): LaCrosse encephalitis virus, St. Louis and West Nile virus, eastern and western equine encephalitis virus
3. pathogenesis -- transferred to human by mosquito bite; multiply at the site, move to blood and lymph nodes; cross brain-blood barrier and infect neurons; eventually stopped by antibody-mediated defenses, but damage can be permanent
4. epidemiology -- transmitted by mosquitoes with birds or rodents at the reservoir; most of those infected apparently do not develop symptoms of encephalitis
5. prevention and treatment -- guard against mosquito bites; vaccines against some versions are available, but generally only given to researchers; there are no approved treatments
2. Some sexually transmitted diseases
1. Bacterial STDs (recall that we have already discussed chlamydia infections)
   
1. gonorrhea -- one of the more common STD's estimated at over 700,000 new cases a year in the US (about 250 cases/100,000 people; reported cases about 1/2 the estimated rate)
1. symptoms -- incubation period of 2 to 5 days; asymptomatic cases possible; in men generally urethritis with discharge containing pus, usually painful; in women, mild symptoms if any
2. causative agent -- Neisseria gonorrhoeae, Gram-negative diplococcus; usually associated with WBC's in smears; must be kept warm and moist so don't do well outside of host; many have R plasmids
3. pathogenesis -- attach to non-ciliated epithelial cells (lining of urethra, uterine cervix, pharynx, conjunctiva) by means of pili or fimbriae (pili can vary within a single clone of gonococci and the genes can be turned off or on (phase variation) so difficult to develop an effective vaccine); cells can destroy IgA associated with membranes; some surface proteins bind to CD4, blocking the ability of cells with CD4 from being activated; in men, inflammation response can lead to blockage of the urethra or inflammation of the testes or prostate; in women, can progress up the fallopian tubes leading to pelvic inflammatory disease, with potential for blockage and increased chances for ectopic pregnancy; in women, also possible to move into the abdominal cavity and attach to other organs; can infect eyes of babies as they pass through the birth canal--eyes must be treated within 1 hour
4. epidemiology --  person to person contact
   
5. prevention -- (k)no(w) sexual partners; condoms reduce the risks (oral contraceptives may increase the risk); no vaccine
   
6. treatment -- antibiotics; widespread resistance to tetracycline and penicillin
2. syphilis -- at one time extremely common (5% of recruits during WWII, now down to less than 5 new cases/100,000; half the primary and secondary cases occurred in 16 counties and 1 city; some bad medical history associated with syphilis as well
1. symptoms -- occur in three stages: primary stage (a hard chancre) appears about 3 weeks after infection, the secondary stage (runny nose, aches and pains, sore throat, rash on soles and palms and sometimes elsewhere) appears 2 to 10 weeks later, the tertiary stage (variable symptoms, including blindness, stroke, mental illness) appears years later
2. causative agent -- Treponema pallidum, a spirochaete; dies readily outside of body; related to causative agent of yaws, another disease with a three-stage progression of symptoms
3. pathogenesis -- multiplies at the point of infection, then spreads to blood and lymph; chancre develops as inflammation response, heals without treatment; secondary stage symptoms the result of antibody-spirochaete complexes at various points; tertiary symptoms result from hypersensitivity reaction to small numbers of bacteria; gumma (granulomatous necrotizing mass) can appear almost anywhere, the damage it represents results in the particular symptoms; the spirochaetes can cross the placenta and infect the fetus (generally after the 4th month)--congenital cases of syphilis are always bad with 40% resulting in miscarriage, others dying of secondary syphilis shortly after birth, still others have characteristic malformations of face, teeth, elsewhere
4. epidemiology -- person to person contact, including kissing if someone in secondary stage
5. prevention -- (k)no(w) sexual partners; condoms reduce the risks (oral contraceptives may increase the risk); no vaccine
   
6. treatment -- penicillin is generally effective
2. Viral STD's
1. genital herpes -- one of the more common viral STD's with at least 45 million infected in the US (about 1/5 of population over the age of 12) and 500,000 new cases each year
1. symptoms -- usually start 1-3 weeks after exposure with itching, burning, and severe pain; blisters form then break after 3-5 days, leaving ulcerated area; ulcers slowly dry out, crust over and heal without a scar; symptoms reappear in an irregular pattern thereafter, usually 4 a year
2. causative agents -- herpes simplex virus II and herpes simplex virus I -- enveloped dsDNA viruses; HSV-I more commonly associated with cold sores; varicella-zoster (chicken pox virus) is very similar
   
3. pathogenesis -- infects epithelial cells, which as virions are released; also infects neurons where the DNA exists as a circle separate from the host's genetic material -- virions can remain latent in neurons for years; if the mother is experiencing a primary case at the time of birth, the baby has a 1/3 chance of contracting an infection, with often fatal or disabling consequences (risk not so high for recurrent symptoms) -- to prevent these infections, infected mothers often deliver by C-section
   
4. epidemiology -- no animal reservoirs; almost all cases by direct person-to-person contact
5. prevention -- avoid period of active symptoms; condoms help reduce risk
6. treatment -- some antivirals can reduced the severity of attacks
2. HIV infections -- first recognized in 1981, now over 900,000 people have been diagnosed with AIDS and 500,000 have died in the United States; currently about 900,000 are living in the US who have been infected by HIV, 200,000 of them are unaware of their infection; world-wide 39 million are living with the infection
1. symptoms -- early symptoms include fever, head and muscle ache, enlarged lymph nodes, rash, all within 6 days to 6 weeks of infection; these are followed at some point by the development of characteristic opportunistic infections and new symptoms including listeriosis,  shingles in more than one dermatome or twice in quick succession, idiopathic thrombocytopenic purpura, persistent diarrhea, PID, peripheral neuropathy, persistent yeast infection (oral or vaginal); full AIDS has additional secondary infections including Kaposi's sarcoma, certain lymphoma's, Mycobacterium infections, cytomegalovirus infections, Pneumocystis carinii pneumonia, Toxoplasma infections of the brain, and others
2. causative agents -- human immunodeficiency viruses, most by HIV-1, in some regions, mostly western Africa, HIV-2 is more common; all are retroviruses, enveloped ssRNA viruses with reverse transcriptase and 2 copies of the genome; major antigens include gp120 (responsible for attachment), gp41 or TM (aids with cell entry), and p17 (maintains structure); the core contains reverse transcriptase, protease, and integrase; protease is necessary because the first two genes are translated as a unit and must be separated to become functional
   
3. pathogenesis -- infect cells with the CD4 receptor (helper T-cells); transcribe their genome into DNA and take up residence in the host's chromosomes (entry into helper T-cells facilitated by chemokine receptors on the cell's surface); the cell is killed during viral replication by a number of mechanisms, including lysis after replication, attack by killer T-cells or natural killers, antibody-mediated cell death, formation of syncytia followed by cell death, or apoptosis; eventually the population of helper T-cells declines to below 200 cells/microliter; macrophages with CD4 are also affected, as are cells in the intestinal epithelium and in the brain;
   
4. epidemiology -- transmitted via blood, semen, vaginal secretions, breast milk, cerebrospinal fluid, synovial fluid, amniotic fluid; virus particles have not been found in sweat; they are found in tears and saliva, but the quantities are probably too low to cause an infection (no known cases of saliva or tears transmitting the disease), however there is a documented case transmission through prolonged open-mouthed kissing involving damage; no transmission through mosquito bites
   
5. prevention -- same as with other STD or blood-borne infection; some success at slowing the spread with condom and needle handouts; mother-to-newborn can often be interrupted by chemotherapy; a few vaccines are in early trials
   
6. treatment -- hit with antivirals, usually a reverse transcriptase inhibitor and a protease inhibitor
3. Some possible secondary infections accompanying AIDS
1. Kaposi's sarcoma -- once used as a diagnostic symptom, now known to be a secondary infection
1. symptoms -- tumors arising from blood or lymphatic vessels in numerous locations
2. causative agent -- herpes simplex virus 8
3. pathogenesis -- attacks endothelial cells, in latent stages the cells change shape and new blood vessels form
4. epidemiology -- common in parts of Africa; in this country only associated with some sort of immunocompromised condition
2. B-lymphocytic tumors in the brain
1. symptoms -- sustained replication of B-lymphocytes
2. causative agent -- Epstein-Barr virus, the causative agent of mononucleosis and involved in the development of Burkitt's lymphoma
   
3. pathogenesis -- presence of HIV causes the activation of latent EBV infections; EBV replicates and infects new B-cells; the infected cells replicate with the virus and have an increased life-span so have lots of cells
   
3. pneumocystosis -- occurs in 4/5 of AIDS cases, one of leading causes of death in AIDS patients
   
1. symptoms -- shortness of breathe and rapid breathing, maybe with a non-productive cough; dusky color; death
2. causative agent -- Pneumocystis carinii, a type of fungus distantly related to yeasts; wall is unusual, so resistant of many antifungals
3. pathogenesis -- spores inhaled into the alveoli, where they attach to the wall
4. epidemiology -- spores are everywhere, apparently everyone has been infected by age 2; only develops into disease in those with weakened immune systems (infants, elderly, immunocompromised)
4. toxoplasmosis -- severe protozoan disease in the unborn and in the immunocompromised
1. symptoms -- in the immunocompetent the symptoms resemble those of mononucleosis (fever, sore throat coated in pus, enlarged spleen); in fetuses can lead to stillbirth, deformities, mental retardation, with the worst symptoms from first trimester infections; in the immunocompromised the symptoms are life-threatening, with encephalitis in about half the cases
2. causative agent -- Toxoplasma gondii, an intestinal protozoan parasite of felines
3. pathogenesis -- humans pick it up either through contaminated food or water (fecal-to-oral route) or by eating undercooked meat with cysts; the protozoan reproduces in just about any mammalian cell with a nucleus; normally quickly brought under control by immune system so that only encysted; if not, then infection is widespread and severely damaging; weakened immune system can also cause the release of previously encysted cells
4. epidemiology -- most adults have been infected, with little harm; immunocompromised are given prophylactic antiprotozoan drugs
5. cytomegalovirus -- another latent disease caused by a herpes virus with severe effects in the immunocompromised
1. symptoms -- in immunocompetent, similar to toxoplasmosis and mononucleosis; in fetuses, there is a bout of jaundice with an enlarged liver, anemia, eye inflammation, and some birth defects--infants without defects may still develop hearing loss and mental retardation; immunocompromised develop widespread symptoms including fever, loss of appetite, joint pain, blindness, paralysis, dementia, coma
2. causative agent -- human cytomegalovirus, enveloped dsDNA (herpes virus)
   
3. pathogenesis -- virus particles enter eye, liver, leukocyte, central nervous system, etc. cells; within the cells becomes latent, slowing reproducing, or productive infection (B and T lymphocytes do not support a production infection unless also infected with HIV); fully productive infections cause cell death
4. epidemiology -- possible that over 85% of adults already infected
   

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