Lecture 16 Biology 115:
Sexually Transmitted Diseases

Spring, 1997 T. Irving: Revised Spring 2000 A. Howard

Objectives

1. Describe how microbes reproduce and how they may become infectious agents.
2. Name the causative agent for AIDS, genital herpes, genital warts, gonorrhea, chlamydia and syphilis
3. Describe the symptoms of a herpes infection
4. Describe methods for preventing the spread of infectious bacteria
5. Describe the symptoms of a gonorrhea infection in the male and in the female
6. Define PID and describe how it effects reproduction
7. Describe the symptoms of chlamydia in the male and the female and compare this disease to a gonorrhea infection
8. Describe the three stages of syphilis
9. Describe how newborns become infected with AIDS, herpes, gonorrhea, chalmydia or syphilis. What effects do these infections have on infants?
10. List other common sexually transmitted diseases and describe the associated symptoms

STD's, like many other diseases, are caused by microbial infections

• Microbes include protozoa, fungi, bacteria and viruses
• Many microbes are harmless or even beneficial
• Bacterial "flora" in gut and on skin
• Bacteria and yeasts used in biotechnology
• Microbes in the soil which recycle nutrients or "fix" nitrogen
• Microbes which cause disease are called pathogens
• Normally benign microbes may cause disease by "opportunistic" growth

Protozoa and fungi:

• are eukaryotic cells i.e. have similar sub-cellular structure to those that make up humans
• Protozoa lack a cell wall. Many are capable of forming cysts that can survive extreme conditions
• Amebic dysentery, giardia, malaria due to protozoan infections
• Fungi may be unicellular (yeasts) or multicellular filaments (molds)
• Fungi and protozoa may make us ill by releasing enzymes and toxins that allow them to invade our tissues
• Examples: Candida (yeast) athlete's foot (mold)

Bacteria are procaryotic cells

• i.e. lack a nucleus and other organelles
• Common forms are bacilli, cocci, and spirilla
• Can occur as individual cells (mono-) or long chains (strepto-)
• Usually have a rigid cell wall
• Some have a slimy external capsule
• Frequently have flagella and rigid projections called pilli
• Pilli help in attachment to cells to be infected
• May form "endospores" which allow them to remain dormant until conditions improve
• Pathogenic bacteria release enzymes and toxins which attack tissues 

Viruses are non-cellular

• Require a host cell in order to make new viruses
• Consist of a nucleic acid core with a protein coats
• Some have an additional membrane -like envelope
• DNA viruses - cause warts, herpes, hepatitis B, mononucleosis, and chicken pox
• RNA viruses cause common cold, flu, AIDS, mumps, measles and polio

Controlling Infectious Bacteria

• Hygiene
• Heat
• Cold
• Freezing
• Drying
• Radiation
• Chemical Treatment
• Disinfectants (surfaces)
• Antiseptics (living tissues)
• Sterilization (autoclave)
• Pressure allows higher temperatures to be reached to kill endospores and viruses
• Antibiotics
• Antibiotics specific to prokaryotic organisms:
  Work by inhibiting specific aspects of bacterial metabolism
• First found in soil microorganisms:
  Antibiotic resistance ( e.g. penicillin-resistant gonococci, TB) serious concern.

Herpes

• Caused by Herpes Simplex II virus
• Similar virus causes cold sores
• Both lie dormant in nervous system
• No cure, symptoms can be relieved by antiviral drugs
• Symptoms include flu-like symptoms, blisters & sores
• Occur within 10 days of infection
• Herpes infection of infants during birth can lead to CNS damage &/or death. C-section birth recommended infected mothers

Genital Warts

• Caused by human papilloma virus
• Highly contagious
• Cause local irritation and itching within 8 months of infection
• Warts then may appear on genitals or mouth and throat
• Strongly associated cervical cancer
• Warts can be removed chemically or surgically

Chlamydia

• Bacterial infection, most common STD in US
• Clamydia bacteria very small - unable to synthesize ATP.
• Like viruses require a host cell to reproduce
• Symptoms occur within 21 days
• Painful urination, vaginal/penile discharge, itching
• Antibiotic treatment usually effective
• Newborns may get eye infections or pneumonia

Gonorrhea

• Bacterial infection (diplococci)
• Very common, chronic and progressive if untreated
• Symptoms appear two-ten days
• Painful urination, vaginal/penile discharge
• Can spread causing heart damage, brain infections, arthritis, skin sores
• Antibiotics usually effective
• No blood test hard to diagnose
• Large fraction of people who get Clamydia, also get gonorrhea - treat for both.
• Penicillin and tetracycline resistant strains exist
• Newborns may get eye infections

Pelvic Inflammatory Disease (PID)

• If Gonococci or chlamydia get established in the oviducts can cause PID
• Especially likely in the case of simultaneous use of IUD
• When inflammation eventually heals, can cause blocking of oviduct
• Likewise can cause blockage of vas deferens in males
• 60-80% of females asymptomatic for gonorrhea
• Disease hard to detect until PID occurs.
• Common cause of sterility

Syphilis

• Caused by a spirochete called Treponema pallidium
• 3 stages separated by dormant periods
• 1st stage
• hard chancre (ulcerated sore with hard edges)
• 2nd stage
• rash can appear all over the body (doesnít itch)
• 3rd stage
• aneurysms
• nervous system
• dementia, blindness, shuffling.
• Gummaís - large destructive ulcers
• Eventually leads to death.

Other STD's

• Trichomonas infection of the vagina (a protozoan)
• Crab lice
• Small arthropods that infect pubic hair causing severe itching
• Not necessarily transmitted sexually
• Can be treated with over the counter medication

AIDS

• AIDS is an autoimmune disease
• Recall "cell mediated immunity"
• Fights off infectious agents, bacteria, fungi, protozoans
• Also abnormal cells in our bodies e.g. cancer cells
• B cells produce antibodies which bind & aggregate them marking them for destruction by macrophages etc.
• Cytotoxic or killer T-cells attack invading cells or host cells infected with viruses directly
• Helper T-cells are required for maturation of B -cells and killer T-cells.
• Helper T-cells are required for a functional immune system
• Without an immune system, normally benign organisms or those that would only cause mild infections are now very dangerous.

Biology of the AIDS virus

• HIV-1 is the AIDS virus
• HIV-1 is a "retrovirus"
• Living organisms have DNA as the genetic material
• (unless you consider viruses to be "alive")
• Retroviruses have RNA as the genetic material.
• Upon infection RNA is copied into DNA which is inserted into the host organismís DNA.
• When these genes are activated, DNA is copied back into RNA, some of which directs synthesis of new viral proteins, some of which becomes new viral RNA.
• HIV buds from the infected cell carrying a part of the cell membrane with it as the outer layer of the cell
• And the cycle repeats.

HIV infection can cause the death of cells in a number of ways:

• Viral infection may cause cytolysis
• Infected cells may be attacked by killer T-cells
• Viral mediated cell fusion (which causes cell death)
• and perhaps other ways.

All retroviruses have at least three genes

• One for the enzyme that converts RNA to DNA
• One for the "core" proteins that package the DNA
• One for a protein that "studs" the outer membrane.
• In addition to these genes, HIV has ~6 other genes
• (pretty complicated for a virus!)
  • One is a "protease" which is necessary for viral protein maturation
  • One is "tat" which stimulates viral transcription
• HIV-1 infects helper T-cells , other types WBCís and some brain cells.
• The glycoproteins on HIV-1 stimulate an immune response from the body but generally not enough to stop infection
• Presence of these antibodies is what is detected in an "AIDS test"

Effect of HIV on T-cells

• When HIV infects helper T-cells it may insert its DNA into the T-cell DNA & remain latent.
• Infection by another virus, bacteria fungus etc. causes the infected T-cell to manufacture more HIV-1
• The HIV-infection grows out of control, T-cells die, the immune system collapses and opportunistic infections overcome the victim
• AIDS victims also very prone to certain kinds of (normally rare) cancers:
  • Possibly 1) Other tumor causing viruses can infect immune compromised host
  • 2) Normal immune system can kill tumor cells but the cancer cells are free to grow if immune system destroyed

Potential AIDS Therapies : Three main directions

1) Anti-HIV drugs.: Most inhibit the RNA-DNA copying step. e.g. AZT

• AZT is a structural analog of one of the 4 DNA subunits (T)
• The viral enzyme copying HIV-1 RNA-DNA will incorporate AZT instead of T into DNA
• DNA synthesis is messed up.
• Viral replication is disrupted.
• HIV-1 RNA mutates rapidly
• AZT resistant strains are out there after prolonged AZT use. - forced selection/evolution
• AZT and related drugs are only moderately effective by themselves

2) vaccines

• Antibodies to HIV-1 are to the surface glycoproteins
• If you inject just the glycoproteins (non-infectious), the body can make lots of antibodies that could fight off a real infection later on.
• Since HIV-1 RNA mutates rapidly, especially that encoding the glycoproteins
• In fact every AIDS patient might have a different HIV strain from every other patient!
• May have several strains at once.
• Since the gene for the glycoprotein changes all the time, the glycoprotein itself
• changes all the time: Very much a moving target
• Vaccines are not generally effective since the strains the vaccine are raised against in the lab may no longer exist when injected in the field.
• The glycoproteins are so different that they are no longer recognized by the antibody

3) New approaches

A) Drugs which strengthen or repair an HIV-damaged immune system

• If cellular immunity (killer T-cells) can be boosted, it may be the most effective part of the immune system for combating HIV
• Interleukin -2 (IL-2) is one drug which may help restore cellular immunity and is now being tested

B) Drugs which target other parts of the HIV life cycle

• Protease inhibitors block the action of the viral inhibitors which are necessary for the maturation of viral proteins and hence intact viruses.
• One could also target tat, a protein necessary for the transcription of viral genes.
• Protease inhibitors in combination with, 3TC (a drug similar to AZT) ( "a cocktail") have significantly improved life expectancy of AIDS patients

Where did HIV-1 come from?

• Best guess is that it arose in the 1950's in central Africa
• There is a distantly related virus in green monkeys which may have somehow entered humans
• The virus then spread to the rest of central Africa, other parts of Africa, then maybe to Haiti, then Europe and America.

How do you get AIDS?

• HIV is not in fact particularly infectious
• HIV may enters the body by way of vaginal,rectal, or oral mucosal membranes.
• Macrophages become infected, move to the lymph nodes where HIV proliferates.
• Can also be passed in the form of infected macrophages, T lymphocytes passed by person in bodily secretions or in blood.
• Unprotected sex with an infected partner is one good way to transmit HIV
• Sharing needles by intrvenous drug abusers is another.

HIV has developed very differently in the third world and in Europe and North America.

• In North America, most cases are in male homosexuals and intravenous blood users.
• In Africa and in many other parts of the world affects mainly heterosexuals
• Very high proportion of prostitutes in major African cities and in Thailand are HIV positive.
• Different strains of HIV responsible
• In America the incidence of new AIDS case s among young people is still rising and is the leading cause of death for males aged 25-44, and the third largest for women in htis age group.
• There is still no cure for AIDS so prevention is the only real option

Avoiding STDs

• Best protection - choose your sexual partners carefully and have few of them.
• Use a latex condom with spermicidal lubricant