Sexually transmitted diseases    Reading pg. 251-275

Introduction

p    Fig. 21.1 Top ten STDs

p    Fig. 21.2 other sexually transmitted diseases

p    Fig. 21.3 Strategies microbes use to overcome host defenses

p   STDs and sexual behavior

n   Spread of STDs is linked to sexual behaviors – can be controlled

p  Asymptomatic individuals play an important role in spread

p  Important determinants

§    Promiscuity

§    Sexual practices

§    Condom usage – retains many microbes

Syphilis

p        Treponema pallidum

n         Spirochete

n         world wide distribution

n         entry through minute abrasions on skin or mucous membranes

n         very sensitive to drying, heat and disinfectants

n         transmission through close contact

n         both horizontal (sexual contact) and vertical spread (through placenta – causes congenital infections)

n         Incubation period is 3 weeks due to slow growth

infectious process

p      three stages of syphilis (fig. 21.6)

n        Primary – hard, painless chancre appears at the site of infection (Usually on the genitalia)

n       secondary often followed by latent period (3-30 yrs)

n       Tertiary – disease stage

T. pallidum: infectious process

p        Survive in host for many years

p        Tissue damage occurs when host responds

n        Respondent cells: plasma cells, macrophages, and polymorphonuclear leukocytes.

p        vertical transmission in utero

n        Congenital syphilis can result in:

p        Intrauterine death of fetus

p        Congenital abnormalities

p        Silent infections – not apparent until 2 yrs of age

laboratory diagnosis

n          difficult, cannot be cultured

n          Microscopy of primary chancre

n          dark field, unstained

n          UV microscopy – stained with fluorescein-labeled anti-treponemal antibodies

n          Serology

n          non-specific tests (fig. 21.7) – non-treponemal antigens

p        2 tests in use:

§        Venereal Disease Research Lab (VDRL) test

§        rapid plasma regain (RPR) test

p        good for screening only

p        False positives occur - confirmed by specific tests

n         specific tests – use recombinant proteins or treponemal antigens to confirm positive result of a non-specific test

p        ELISA – detects IgA and IgG

p        fluorescent treponemal antibody absorption (FTA-ABS) (fig. 21.8)

p        T. pallidum hemagglutination assay (MHA-TP)

serology

n         passive antibody

n         Transferred from mother or baby’s own

n         several tests necessary for confirmation of syphilis

n         penicillin is drug of choice for treating syphilis

n         Preventative as well as curative of congenital syphilis if administered early in pregnancy

Gonorrhea

p        Neisseria gonorrhoeae

n         gram negative diplococci

n         Human reservoir, transmitted by direct contact (sexual)

n         sensitive to drying - intimate, direct contact required for transmission

n         major reservoir of infection is asymptomatic individuals (almost always women)

n         vertical transmission during childbirth resulting in ophthalmia neonatorum

p        Prevented with silver nitrate or erythromycin within 1 hour of birth

n         Site of entry: vagina, penis, throat or rectum

p        has developed several attachment mechanisms (fig. 21.9)

n         virulence factors facilitate spread

n         spread is through the cervix in women and up the urethra in men

n         host damage due to host's immune response

n         Symptoms:

p        Males: urethral discharge and dysuria

p        Female: thrives in cervix and fallopian tubes

§        may develop pelvic inflammatory disease (PID)

§        asymptomatic in most women but risk of ectopic pregnancy and infertility

n          infection is usually localized but can become systemic (fig. 21.12)

Laboratory diagnosis

p        Urethral and vaginal discharge by:

n         Microscopy

p        Gram negative intracellular diplococci

n         Culture –

p        Modified Thayer Martin (selective for Nesseria sp.)

p        Chocolate blood agar (enriched – isolation of fastidious pathogens, Neisseria and Heamophilus)

Treatment

p        Antibacterial agents used: penicillin, ceftriazone, ciprofloxacin, spectinomycin

p        eye drops for babies of infected mothers

p        Early treatment of sexually promiscuous individuals à reduced infectiousness and transmission rates

p        resistance is increasing

p        No vaccines

p        Use of condoms can prevent infection

Chlamydial Infection

n       Chlamydia trachomatis

n       Obligate intracellular parasites

n       fig. 21.14 Medically-important Chlamydiaceae

n         Exist in two forms:

n         elementary body (EB) is extracellular form as well as infective form

n         reticulate body (RB) is intracellular and replicative form

n         Causes asymptomatic infections common in women

n         Genital infections - acquired during sexual intercourse

n         Ocular infections – autoinoculation from infected genitalia

n         passed to neonates during birth causing ocular infections and/or pneumonia

n         enters through abrasions in mucosal surface

n         Fig. 21.13 Lifecycle

n       clinical effects due to cell destruction and host’s immune response

n       fig. 21.15 Clinical syndromes caused by C. trachomatis

n        laboratory diagnosis

n         cell culture

p         stain with iodine to see characteristic inclusion bodies

p         immunofluorescent stains

n         direct antigen detection in clinical specimen by fluorescent microscopy

n         Nucleic acid-based tests - detection of pathogen DNA

n        treatment and prevention - doxycycline or tetracycline

n        Beta-lactam antibiotic – no effect on Chlamydia

n        Multiple antibiotics may be used

n        Babies - erythromycin

Other pathogens that cause lymphadenopathy

p         Besides syphilis and gonorrhea

p         Lymphadenopathy:

n          swelling of lymph nodes in groin

1.    Chlamydia trachomatis, serotypes L1, L2  and L3

n          occurs primarily  in Africa, Asia and South America

n          systemic infection with lymphoid involvement

p        Lesion at site of infection

p        Infection of lymph nodes - inguinal buboes

n          Frei test is diagnostic tool

n          cell culture possible – isolate rate is low

n          treatment is doxycycline or tetracycline

2.    Haemophilus ducreyi

n       Pleomorphic Gram negative rod

n       causes chancroid

p      single or multiple genital ulcers

p      Sores are soft chancres

§      Unlike hard chancres of syphilis

p      swollen groin lymph nodes

§      Often pus filled

p         Pathogenesis

n         Pimple appears at site of entry à ulcers

n         Organisms reach lymph nodes à immune response

p         Laboratory diagnosis

n         Microscopy – gram-negative rods in chains

n         Culture on rich medium - difficult to grow

p         Epidemiology

n         Epidemics generally associated with prostitution

n         Lesions promote AIDS transmission

p   Prevention and Treatment

n   Safe sex practices decrease risk

n   Chancroids respond well to antibiotic treatment

p  Erythromycin and ceftriaxine

p  Some strains resistant

3.    Calymmatobacterium granulomatis

n          Causes Donovanosis

p        Bacteria multiply inside mononuclear cells à rupture to release bacteria

p        Characterized by nodes on genitalia à granulomatous ulcers

n          Common in tropical and subtropical regions

n          Diagnosed by microscopy:

p        see Donovan bodies - clusters of blue or black stained organisms inside mononuclear cells

n          Treatment: tetracycline or cotrimoxazole

n          Donovan bodies

Mycoplasmas and Non-gonococcal urethritis

p    May cause genital tract infections

p    Not certain if transmission is sexual

Other causes of vaginitis and urethritis

n         Candida albicans

n         Part of vaginal normal flora in ~35% of women

p        when increase in population à yeast infection, vaginitis (irritation and curd-like discharge)

n         Males: causes balanitis (inflammation of glans of penis)

n         Diagnosis:

p        microscopy and culture

n         Treatment:

p        oral or intravaginal treatment

     with antifungal medication

n         Trichomonas vaginalis

n         Flagellated protozoan

n         Causes trichomoniasis

n         Transmitted during sexual intercourse

p        Inhabits vagina in women, urethra and prostate of men

p   Symptoms

n   symptomatic in women

p  Itching, redness and burning of vagina

§    due to trauma of moving protozoan

p  Frothy malodorous yellowish-green discharge

§    due to gas production by organism

n   asymptomatic in most men

p  Some have penile discharge, pain on urination, painful testes or tender prostate

p   Diagnosis:

n   microscopy examination of discharge

p  see motile trophozoites

p    Prevention and Treatment

n    Abstinence, monogamy and use of condoms

n    Treatment with metronidazole (flagyl)

n          Gardnerella vaginalis

n          Causes bacterial vaginosis; sexually transmitted

n          Characterized by:

p        Excessive malodorous discharge (fishy odor)

p        Decrease in vaginal acidity

p        Derangement of normal vaginal flora

p        Presence of “clue cells” (bacteria coated vaginal cells)

n          Diagnosis:

p        microscopy and culture

n          Treatment:

p        metronidazole

Genital Herpes

n           primarily caused by HSV II

n          Causes vesicles on penis or vulva

p         breaks down to form ulcers

n          HSV-1 – cold sores

n           diagnosed by clinical appearance

n          Immunofluorescence using monoclonal antibodies

n          HSV DNA detection

n           treatment

n          no cure

n          antiviral medications decrease severity of lesions

p         Oral – acyclovir, valacyclovir, famacyclovir

p         Intravenous acyclovir - systemic complications

p          Most patients will have recurrence

n          lifelong risk of transmission even in absence of symptoms

Human Papillomavirus

p    Transmitted sexually

p    Associated with cervical cancer

p    Causes:

n    warts on penis, vulva and perianal region

n    Precancerous lesion on cervix (asymptomatic)

p   detected with vaginal exam and pap smear

§    Multi-nucleated cells

p   removed by laser

n    risk factor - history of multiple sex partners

n    Treatment with podophyllin (caustic resin)

n    Prevention:

p   vaccine (Gardasil)

p   HPV test

AIDS (acquired immunodeficiency syndrome)

p    first reported in United States in 1981

n    1983 – fully sequenced

p    worldwide epidemic killing > 25 million people.

n    > 900,000 reported cases in US since 1981

p    Causative agent:

n    Human immunodeficiency virus (HIV)

p   Most US cases causes by HSVI

p   Most African cases caused by HSVII

n    retrovirus: enveloped, single-stranded RNA, reverse transcriptase

p   Pathogenesis

n   HIV attacks Helper T-cells

p  progressively destroys body's immune system and its ability to fight life-threatening diseases (opportunistic infections).

n   HIV replication cycle

p    Symptoms

n    flu-like illness within a few months

p   Fever

p   Head and muscle aches

p   Enlarged lymph nodes

p   Rash

p    symptoms disappear within a week to a month.

n    remain very infectious

n    large quantities of HIV in genital fluids.

p    "asymptomatic" period may last for 10 years or more

n    virus is actively multiplying, infecting, and killing cells of the immune system.

p    Epidemiology

n    HIV - spread mainly through unprotected sex

p   Enter through vagina, vulva, penis, rectum, mouth

n    Contaminated needles – drug users, tattoo, body piercing

n    from mother to newborn

p   during pregnancy or birth

p   through breast milk

n    Virus not highly contagious outside of risk factors

n    Transmission can be halted by changes in human behavior

Diagnosis

p    blood test for presence of antibodies.

n    ELISA and Western Blot.

p    Molecular analysis: PCR

p    Early testing:

n    early treatment to help immune system combat HIV à prevent emergence of opportunistic infections

n    alerts against high-risk behaviors that could spread virus to others.

Prevention

n    Interruption of mother to child transmission via chemotherapy and C-section

n    abstain from having sex

n    avoid risky behaviors:

p   sharing needles (Needle exchange programs)

p   Avoid exposure to blood products

p   having unprotected sex

n    Public educational programs targeting risk populations

n    Vaccines – challenging, but hopeful

Treatment

p   No cure

p   Medications

n   available to prolong life

n   designed to block replication of HIV

n   generally cocktails of different drugs

p        drugs used to treat HIV infection

n         nucleoside reverse transcriptase (NRT) inhibitors

n         non-nucleoside reverse transcriptase inhibitors (NNRTIs)

p        Both interrupts reverse transcriptase (prevents virus making copies of itself).

p        slow spread of HIV in body

p        nucleoside analogs (AZT)

n         protease inhibitors

n         Interrupt assembly of virions.

n         fusion inhibitors (Fuzeon)

n         works blocking fusion of virus with cell membranes.

p        blocks HIV's ability to enter and infect the human immune cells.

p   HIV can become resistant to these drugs

n   combination treatment effectively suppresses virus

n   highly active antiretroviral therapy (HAART)

p  Reduce number of deaths from AIDS in this country.

p  not a cure for AIDS

p  has greatly improved health of people with AIDS