MBI 111 Microorganisms and Human Disease

Diseases Transmitted by Genitourinary Infection

Background

• Anatomy and associated host defense factors
  • urinary tract (male and female) - urethra, bladder, ureters and kidneys
    • physical - mucus, epithelium (barrier), flushing with urine
    • chemical - mucus, low pH of urine
    • cellular - phagocytes (PMN), normal urethral microbiota
  • genital tract (male) - urethra (see above), seminal ducts
    • physical - mucus; epithelium
    • chemical - mucus
    • cellular - PMN
  • genital tract (female) - vagina, uterus, fallopian tubes
    • physical - mucus; multi-layered, continually-sloughing epithelium
    • chemical - mucus; low pH (lactic acid produced by normal microbiota)
    • cellular - phagocytes (PMN); normal microbiota (live on sloughing epithelial cells, which contain glycogen) maintain pH ~3-4
  • external genitalia (male and female)
    • physical - barrier
    • chemical - mucus, specialized sebaceous secretions (smegma, etc.)
    • cellular - normal microbiota
• Epidemiology
  • etiology
    • urinary tract infections - normal microbiota; exogenous microbes
    • genital tract infections - normal microbiota; exogenous microbes contracted during sexual intercourse
  • predisposing factors
    • sexually transmitted diseases (STDs) - sexual promiscuity
    • non-STDs - poor personal hygiene, incomplete urinary flushing, catheterization
  • general STD Information
    • The latest estimates indicate that 15 million Americans become newly infected with an STD each year, yet they remain one of the most under recognized health threats.
    • STD Hotline - (800) 227-8922
    • AIDS Hotlines - (800) 342-2437

Genitourinary Tract Diseases

• Urinary Cystitis
  • epidemiology: Escherichia coli (bacterium) causes 85% of cases ... the rest are caused by other normal (GI tract) microbiota; associated with sexual intercourse, but not an STD; mostly affects women; ~7 million cases/year in US
  • pathogenesis: urethral, then bladder damage causes inflammation (may also cause abscesses) which lead to dysuria (pain, urgency, frequency, pyuria, hematuria); complications include pyelonephritis, an infection that ascends to kidneys causing pyelonephritis (~250,000 cases/year in US) which involves renal damage, fever, chills, vomiting, nausea, diarrhea, deep abdominal pain, leukocytosis, and may lead to chronic infection with scarring and fibrosis
  • treatment: sulfa drugs, ampicillin, tetracycline, nitrofurans, naladixic acid plus antispasmodics ... people in the US spend $1 billion per year to treat this disease
  • prevention: avoid urethral contamination, urethral flushing, low urine pH
• Vaginosis
  • epidemiology: Candida albicans (fungus); Gardnerella vaginalis (bacterium); Trichomonas vaginalis (protozoan) - opportunistic normal microbiota, but may be transmitted by sexual contact; ~5 million new cases estimated per year in US (~300 thousand cases of trichomoniasis reported per year in US; frequently occurs together with gonorrhea)
  • pathogenesis: vaginal infection causes tissue damage and leads to vaginitis characterized by inflammation that causes itching, along with:
    • dry, red epithelium and a white (may be yellowish), curdy discharge (exudate) that smells "yeasty" (Candida)
    • pink epithelium and an abundant, gray-white, thin and frothy discharge (exudate) that smells "fishy" and contains "clue" cells (Gardnerella)
    • red and tender epithelium and abundant greenish-yellow frothy discharge (exudate) that smells "foul" (Trichomonas); complications may include premature birth; males may get urethral and/or prostatic Trichomonas infection that may cause painful urination with thin mucoid discharge, but is generally asymptomatic
  • treatment: Candida - clotrimazole, miconazole or nystatin; Gardnerella - metronidazole, sulfa drugs; Trichomonas - metronidazole, tinidazole or miconazole (both the patient and her/his sexual partner(s) should be treated)
  • prevention: personal hygiene for prevention of Candida and Gardnerella infections; avoid promiscuity and use condoms for best prevention of Trichomonas infections
• Toxic Shock Syndrome (TSS)
  • epidemiology: Staphylococcus aureus (bacterium - normal microbiota in ~30% of humans) or Streptococcus pyogenes (bacterium); ~10 cases reported per year in the US (most associated with tampon usage; some associated with skin infections now) but CDC thinks they are vastly underreported (perhaps as many as 1300 per year?)
  • pathogenesis: enterotoxin in bloodstream (toxemia) causes systemic damage throughout the body, leading to high fever, vomiting, diarrhea, shock and characteristic rash; complications include death in about 5% of cases (if not treated with appropriate antimicrobial agents)
  • treatment: fluid replacement therapy and antimicrobial agents (cephalosporins, vancomycin)
  • prevention: use low absorbancy and non-bleached tampons; change tampons frequently
• Gonorrhea
  • epidemiology: Neisseria gonorrhoeae (bacterium); 358,995 cases reported in the US in 2006 (this STD is thought to be under-reported by at least a factor of 2); this is a ~70% decrease since 1975; prevalence is equivalent in men and women and is higher in blacks than whites, and is highest in the southern states
  • pathogenesis: 2-4 day incubation period:
    • males - urethritis leads to dysuria, discharge (10-20% asymptomatic); complications include arthritis
    • females - cervicitis (+/- urethritis) leads to cervical lesions (+/- dysuria) (~80% of cases are asymptomatic); complications include pelvic inflammatory disease (PID) which is painful and often leads to infertility (~50,000 US women develop PID-related infertility each year); arthritis; congenital infections of newborns (ophthalmia neonatorum)
  • treatment: cefixime (Suprax), ceftriaxone (Rocephin), ciprofloxacin (Cipro) and ofloxacin (Floxin) (~25% of these bacteria are resistant to penicillin, tetracycline or both these CTAs); ciprofloxacin is used in double-resistance cases; cure does not preclude re-infection
  • prevention: avoid promiscuity, use condoms; screening combined with effective treatment; silver nitrate or erythromycin ointment in infant's eyes to prevent ophthalmia neonatorum
• Chlamydial Disease
  • epidemiology: Chlamydia trachomatis (bacterium); most frequently reported infectious disease in the US ... 1,030,911 cases reported in 2007, but an estimated 4+ million infections occur annually; prevalance is 5 times higher than in 1987 (mostly due to increases in detection, not incidence), with highest incidence in the south; rates in women are about 5 times greater than in men; women aged 15-19 account for 46% of cases, and women aged 20-24 account for 33% of cases
  • pathogenesis: variable incubation period (generally 7-21 days):
    • males - asymptomatic (~50%) or urethritis with dysuria and whitish discharge (sometimes lumped together with other, similar conditions and called nongonococcal urethritis (NGU); complications include swollen and tender testicles
    • females - cervicitis with vaginal discharge (sometimes with bleeding) and may also have dysuria, although most cases (~75%) are asymptomatic; complications include:
      • 3-5 times higher chance of getting HIV infection, if exposed to HIV
      • PID (in up to 40% of women with untreated chlamydia) which leads to debilitating, chronic pelvic pain in 18% of cases, and may lead to potentially-fatal ectopic pregnancy (9% ... leading cause of first-trimester, pregnancy-related deaths in American women), and/or infertility (20%), premature delivery, postpartum morbidity, neonatal conjunctivitis, and pneumonia

    (Note: There is also a more virulent form of Chlamydia trachomatis that causes lymphogranuloma venereum (LGV) in either males or females.)

  • treatment: erythromycin, tetracycline, ofloxacin (fluoroquinolone), doxycycline, azithromycin (single dose); must treat symptomatic patient and all sex partners (whether symptomatic or not); annual cost of treatment of US chlamydial disease patients is ~$2.4 billion
  • prevention: use condoms, avoid promiscuity; all sexually active females should be tested for Chlamydia during a pelvic exam at least annually; screening associated with effective treatment would minimize transmission and is estimated to cost ~$175 million annually in the US; silver nitrate or erythromycin ointment in infant's eyes to prevent ophthalmia neonatorum
• Syphilis
  • epidemiology: Treponema pallidum (bacterium); during World War II, there ~600,000 cases were reported in the US; since then, incidence has declined 87% to 36,935 cases of syphilis (all stages) reported in 2006 of which 9,756 were newly-acquired primary or secondary cases, and 349 were new congenital cases; incidence is highest in southern states and is 34 times higher in blacks than whites; unfortunately, there are 2 cases of latent syphilis for every primary/secondary case reported in the US; women tend to get syphilis at an earlier age than men
  • pathogenesis:
    • Syphilis has three active stages (primary, secondary, tertiary) with a variable-length latent period between the secondary and tertiary stages
      • primary - chancres develop at the site of infection within 10-90 days (average is 21 days) after infection; they last 1-5 weeks and clear up without treatment (although the disease continues to develop)
      • secondary - papulosquamous lesions develop 2-12 weeks after chancres; may appear as nickel and dime lesions on face or mucous patches inside the mouth; these rashes last 2-6 weeks and clear up without treatment (although the disease continues to develop); additional signs and symptoms include fever, swollen lymph glands, sore throat, patchy hair loss, headaches, weight loss, muscle aches, and tiredness
      • latent (hidden) period - no obvious signs and symptoms, but the host is still infected and further disease may develop as the bacterium begins to damage internal organs including the brain, nerves, eyes, heart, blood vessels, liver, bones, and joints; about one-third progress to tertiary syphilis
      • tertiary - gummas develop 3-10 years after secondary lesions disappear, these develop in a number of tissues besides the skin, and result in damage to cartilage and bone, joints (arthritis), heart and blood vessels, and brain
    • complications -
      • tertiary stage disease signs and symptoms
      • genital sores caused by syphilis in adults also make it easier to transmit and acquire HIV infection sexually
      • untreated syphilis during pregnancy results in a 40-70% chance of the baby being infected (congenital syphilis), causing skin sores, very runny nose (sometimes bloody and infectious), slimy (mucous) patches in the mouth, inflamed arm and leg bones, swollen liver, jaundice, anemia, small head, retardation, seizures, death (~12% ); over 65% of cases of congenital syphilis are among African Americans
  • treatment: penicillin (dependent upon how long the patient has had syphilis ... single dose if less than 1 year) kills the bacterium and stops the infection (together with the immune system) but cannot reverse the damage already done; cure does not prevent re-infection
  • prevention: use condoms, avoid promiscuity
• Genital Herpes
  • epidemiology: Herpes Simplex Virus 2 (HSV-2) is transmitted by direct contact, with or without the presence of sores or other symptoms; there are ~500,000 new cases of this STD per year in US leading to a total of ~45 million people ages 12 and older (1 in 5 in the adolescent and adult population) who are infected with HSV-2 and ~30% of US adults have anti-HSV2 antibodies; genital herpes is 3 times more prevalent in blacks than in whites, but rates of increase are highest in young white teens; unfortunately, ~80% of those infected aren't aware they are, so they spread it around unknowingly; more herpes information
  • pathogenesis: although some people have very mild signs and symptoms, recurrent chronic painful genital lesions (ulcers or blisters) typically develop within 2-20 days (generally in 2 weeks) and usually heal in 2-4 weeks; lesions may be accompanied by flu-like symptoms, including fever and swollen glands; recurrence (4-5 times during first year of infection) is induced by stress, colds, other febrile illness, etc.; complications include:
    • spreading of lesions to surrounding skin
    • causative factor in cervical cancer
    • psychological stress
    • lesions make people more susceptible to HIV infection, and HIV-infected people with herpes transmit HIV more readily
    • infection of newborns during delivery leads to encephalitis, blindness, meningitis, disseminated necrotic skin lesions; this can be avoided by cesarean-section delivery
  • treatment: acyclovir, famvir, or valtrex shorten disease episodes, slow recurrence, but don't cure (due to asymptomatic nature of most cases, testing is needed before treatment begins)
  • prevention: use condoms, avoid promiscuity; vaccine (still experimental and protects women, but not men ... and only works if they have not been previously infected with other herpes viruses)
• Genital Warts (Condylomata acuminatum)
  • epidemiology: Human Papilloma Viruses (HPV); 30 types of HPV can be transmitted during sexual intercourse via cuts or abrasions; ~5.5,000,000 new cases per year in US
  • pathogenesis: growth of viruses in cells causes warts (chronic benign tumors) on genitalia (may also occur on mouth, anus, urethra, bladder); HPV types 6 and 11 cause ~90% of genital warts; complications - disfiguring; secondary bacterial infections; HPV types 16 and 18 cause ~70% of cervical cancer cases (more than 90% of women with cervical cancer test positive for HPV) and are linked to penile cancer, both of which are more prevalent among those who begin having sexual intercourse at an early age and have many sexual partners
  • treatment: remove wart using:
    • drugs such as imiquimod cream, which stimulates the immune system to fight the virus, or those that directly remove the wart tissue, such as podophyllin or trichloroacetic acid
    • surgery ... laser surgery, cryosurgery or electrolysis
  • prevention: Gardasil vaccine protects against HPV types 6, 11, 16 and 18 ... and must be given prior to contact with them to be effective; it is recommended for females age 9-26, but is more likely to be effective if given at the earliest ages (prior to initiation of sexual interactions); Gardasil has recently been shown effective in males as well as females; use condoms, avoid promiscuity
• Hepatitis B, C and D
  • epidemiology
    • Hepatitis B Virus - hepatitis B is transmitted by sexual (especially in men who have sex with men) contact (55% of infections) and IV drug injection, transfusion, tatoos, and can be transmitted from mother to infant during the process of birth; ~5,000 cases reported each year in US, but CDC estimates actual infections may be as high as 20,000 per year with as many as 1.25 million chronic cases in the US and 200-300 million cases worldwide
    • Hepatitis C virus - hepatitis C is transmitted in the same ways as hepatitis B (injection of illegal drugs, transfusion, tatoos or engaging in unprotected sex); ~800 new reported cases of hepatitis C per year in US, but CDC estimates actual infections may be as high as 20,000 per year with ~3.2 million chronic cases in US and ~100 million cases worldwide
    • Hepatitis virus D - defective virus (may be a viroid) that only infects hepatitis B victims; hepatitis D is primarily transmitted via infected blood; CDC estimates there may be ~70,000 carriers in US
  • pathogenesis:
    • hepatitis B - 50% asymptomatic, but in the other 50%, liver infection leads to fatigue, anorexia, taste changes, vomiting and jaundice (indicating liver damage); complications include damage to intestines (clay-colored stools), and kidney (dark urine); chronic disease, carriers (6-10%); cirrhosis; hepatitis D virus co-infection; death (~5,000 per year in US)
    • hepatitis C - 70% asymptomatic, 30% have mild symptoms; complications include chronic liver infection, carrier state (~40%); cirrhosis; risk factor for hepatocarcinoma; death (~10,000 per year)
    • hepatitis D - only infects those who are already infected with hepatitis B virus, but makes these cases more severe because it causes progressive liver damage; death (20-30%, ~1000 per year)
  • treatment: α-interferon for hepatitis B and C; TLC (prolonged bed rest); liver transplant
  • prevention: avoid high-risk behavior; use condoms; get hepatitis B vaccine; hepatitis B immune globulin for those who have been exposed, but have not yet exhibited signs or symptoms of disease
• Acquired Immunodeficiency Syndrome (AIDS)
  • epidemiology:
    • Human Immunodeficiency Virus (HIV) is transmitted by entrance into the bloodstream via body fluids (blood, semen, vaginal secretions, breast milk) from an infected host
    • HIV originated in Africa (as early as the 1940s or 1930s ... and there is controversy about when and how it got into humans), then spread to the US and throughout the world primarily via promiscuous sexual behavior and IV drug abuse (shared needles)
    • 58 million people have been infected with HIV since 1981, more than 80% of whom were infected by heterosexual intercourse
      • 5 million new HIV infections last year ... 14,000 infections per day (95% are in developing nations)
      • 40 million people are now infected ... 37.2 million are adults (and 48% of them are women ... ~80% of all HIV infections (worldwide) are contracted via heterosexual intercourse)
      • ~95% of the people with HIV infection live in the developing world
        • Sub-Saharan Africa is hardest hit region, with 28.1 million HIV-infected people ... 70% of the total (4.7 million in South Africa alone)
        • South and Southeast Asia is next hardest hit, with 6.1 million HIV-infected people ... 15% of the total
      • 22 million people have died of AIDS so far ... ~3 million last year, one-sixth of whom were under 15
    • 793,026 cases diagnosed in the US and reported between 1981, when AIDS was first recognized as a specific disease, and the end of June 2001 (most current data available) ... and more than 457,667 (58%) of diagnosed AIDS patients have already died
      • 40,894 new cases were diagnosed in adults/adolescents (70% in men; 30% in women) and 196 new cases were diagnosed in children/infants during 2000-2001
      • 15,245 people died of AIDS during 2000-2001 in the US
        • ~50% were black, ~30% were white, ~18% were Hispanic
        • ~67% drop in annual number of deaths from AIDS between 1995 and 1999)
      • 351,518 people were living with AIDS in the US at the end of 2000 ... 79.4% of them were men and 76.8% of them were 35-64 years old (20.1% are 20-34)
      • most cases are in large cities
      • AIDS is no longer one of the top 15 killers in the US ... this is down from number 8 in 1995 and from number 14 in 1997 ... but AIDS is still the:
        • number 9 killer of people aged 15-24
        • number 5 killer of people aged 25-44 (leading cause of death for black men in this age group)
        • number 10 killer of people aged 45-64
      • 800,000-900,000 US residents are estimated to be living with HIV infection ... and 1/3 of them don't know they are infected ... the largest percentage live in the south
      • ~10,000 cases and ~6,000 deaths in Ohio, mostly in large cities ... Ohio ranked 35th the US last year in new HIV cases reported
      • males account for 77% and females for 23% of AIDS cases in the US (570,425 cases diagnosed in adult males; 109,311 cases in adult females; 8,461 cases in children under age 13)
      • females are the most rapidly rising incidence group ... 23% of AIDS cases reported last year (up from 7% in 1985)
      • 98% of AIDS victims in the US have been more than 20 years old (1% ... less than 12; 0.5% ...13-19; 17% ... 20-29; 45% ... 30-39; 26% ... 40-49; 11% ... 50+) at diagnosis
      • AIDS incidence is disproportionately high in lower socioeconomic groups ... overall (last year) whites accounted for 33%, blacks for 45%, and hispanics for 20% of cases ... despite the fact that the US population is comprised of whites 71%, 12% blacks and 13% hispanics ... graph of history
        • among men, blacks account for 50%, whites for 30%, and hispanics for 20% of newly-infected cases
        • for newly infected women, approximately 64 percent are black, 18 percent are white, and 18 percent are Hispanic
    • AIDS incidence by exposure category
      • white men who have sex with men were the first AIDS victims in the US, followed closely by IV drug abusers, and then by recipients of blood products, but this has continued to change significantly during 21st Century, as exemplified by the following transmission pattern for adults last year:
        • sexual transmission
          • men who have sex with men (MSM) - 45% of all AIDS diagnoses
            • 60 percent of men who were infected with HIV were infected as a result of having sex with men
          • heterosexuals - 14% of all AIDS diagnoses
            • 62% of women with AIDS got it via heterosexual intercourse
            • worldwide, 75% of HIV infections have been transmitted by heterosexual intercourse
        • intravenous transmission
          • IV drug users (IDU) incidence is racially-biased
            • MSM who use IV drugs - 4% of all AIDS diagnoses
            • not MSM - 23% of all AIDS diagnoses
            • 25 percent of men and 25 percent of women were infected through injection drug use
          • transfusion or organ transplant recipients - 1% of all AIDS diagnoses
          • hemophiliacs - less than 1%
        • undetermined transmission - 23% of all AIDS diagnoses ... but these cases generally distribute themselves among the top four groups listed above
      • heterosexual AIDS victim percentages are increasing rapidly while those of MSM AIDS victims decline
    • AIDS health care costs in the US are currently more than $45 billion per year, and this epidemic continues to seriously strain the US medical community and its infrastructure
  • pathogenesis: HIV infects and kills T lymphocytes (CD4 T cells) which leads to this progression of signs and symptoms
    • flu-like syndrome (malaise, fatigue, headache, fever, chills, lymph node swelling) ~2 weeks after infection ... antibody response within subsequent 2-6 months allows detection of HIV+ status
    • progressive generalized lymphadenopathy (PGL) follows ... characterized by lymph node swelling and occasional opportunistic infections
    • AIDS develops in more than 34% of HIV+ people within 1-15 years after HIV infection
      • CD4/CD8 T cell ratio decreases due to selective loss of CD4 T cells
      • Kaposi's sarcoma (cancer that affects blood vessels) and/or cervical cancer, wasting syndrome (massive weight loss), and multiple opportunistic infections develop as a result of this immunocompromise, including
        • pneumocystis pneumonia (PCP)
        • tuberculosis
        • histoplasmosis
        • candidiasis (oral or vaginal)
        • toxoplasmosis
        • cryptosporidiosis
        • strongyloidiasis
    • death eventually results from a combination of overwhelming opportunistic infections, cancer and wasting syndrome
  • treatment:
    • combination ("cocktail") therapy using two nucleoside analogs and one protease inhibitor
      • nucleoside analogs inhibit reverse transcriptase, an enzyme whose activity is critical to HIV replication; a typical combination might be Retrovir (zidovudine, azidothymidine, AZT) given together with Videx (dideoxyinosine, didanosine, ddI)
      • protease inhibitors inhibit the function of an enzyme needed for final processing of HIV proteins to allow nucleocapsid assembly; examples include Invirase (saquinavir), Norvir (ritonavir) and Crixivan (indinavir)
    • this combination of drugs:
      • inhibits replication of HIV at two different points, so the combination is much more effective than any of the drugs given alone
      • prolongs life, thus greatly decreasing death rates in prosperous nations, but does not cure HIV infection or AIDS
  • prevention:
    • avoid contact with potentially-infected persons (abstinence; use condoms; no promiscuity)
    • potential vaccines are being developed in many laboratories ... none has proven effective as yet, though
    • article about US proposals to combat AIDS on a global basis

For more information on AIDS and other STDs ...

• General STD Information
  • The latest estimates indicate that 15 million Americans become newly infected with an STD each year, yet they remain one of the most under recognized health threats.
  • STD Hotline - (800) 227-8922
  • AIDS Hotlines - (800) 342-2437 
• Afraid to ask ... about STDs?
• Common STDs and the Organisms That Cause Them
• Nothing but the Facts ... about STDs
• Assess Your Risk for AIDS and Other STDs
• CDC National AIDS Hotline
  • (800) 342-2437
  • (800) 344-7432 (Spanish)
  • (800) 243-7889 (Deaf Access)
• CDC's National Prevention Information Network
  • (800) 458-5231
  • PO Box 6003, Rockville, MD 20848-6003
• CDC Statistics Hotline - (800) 232-3228 ... for statistics about HIV/AIDS that will be faxed to you within 24 hours
• For Questions and Concerns Regarding Public Policy ...
  • AIDS Action Council - (202) 986-1300
  • National Association of People with AIDS - (202) 898-0414
  • National Minority AIDS Council - (202) 483-6622
• AIMS Media - (800) 367-2467 ... for educational videos aimed at young children, parents, and teens, regarding HIV/AIDS
• Clinical Trials Information Service - (800) 874-2572

A Guide to Safer Sex

• Be selective: Know your partner well before you have sex and learn to recognize a high-risk sex partner. Drug users who share needles, men who have sex with men, and persons who have had multiple sex partners are more likely to share AIDS or other STDs with you.
• Limit your sex partners: The fewer people you have sex with, the lower your chance of catching STDs or AIDS. The more partners you have during your lifetime, the more likely you are to be exposed to infectious agents that lead to cancer of the cervix or penis. You can cut your risks by starting sex later in life.
• Use condoms: Condoms help prevent both STDs and pregnancy; they should be used until both of you have had two consecutive negative HIV tests (about six months after ceasing to have other partners) for all sexual intercourse between partners who have had other sex partners.
• Do what's safest: Although abstinence is the surest way to avoid AIDS or other STDs, hugging and kissing aren't likely to spread them. Vaginal intercourse is the safest form of sex.
• Make sex good by doing only what feels right: Never let yourself be forced; never force anyone else. If it hurts or causes bleeding, don't do it.
• Get tested: If you have a new sex partner or have had more than one partner in six months, you should both be checked for HIV infection (and for STDs such as gonorrhea, chlamydial disease and syphilis).
• Watch for genital sores or unusual discharges: If either of these appears, get a checkup right away.

Have fun studying this new micro stuff, and be sure to check out the sample questions for exam 3!