Sexually Transmitted Diseases

Question 1

Signs or Symptoms of STIs

Answer 1

– typically NO SYMPTOMS
o Men and Women – sores/bumps/blisters near genitals/mouth; burning when urinating; fever/chills/aches; swelling of genital lymph nodes; frequent urination
o Men Only – drip/drainage from penis
o Women Only – vaginal discharge or odor; pain in lower pelvis or deep in vagina; burning or itching; bleeding from vagina at time other than menses

Question 2

Trichomoniasis

Answer 2

– trichomonas vaginalis
o Protozoan; 7 million per year
o Most carriers experience no symptoms
 Female more likely to have vaginitis; males may have urethritis (less often)
o Symptoms: foamy, yellowish, unpleasant smelling discharge, burning sensation, itch, painful urination and intercourse
o If untreated, increases risk of other STIs and preterm/low birth weight
o Pregnancy – preterm delivery and low birth weight
o Mechanism: sexual contact; toilet seats, wet towels, or other items w/ discharged fluids
o Diagnosis: swab and wet mount slide or PCR
o Treatment: oral metronidazole

Question 3

Chlamydia

Answer 3

– chlamydia trachomatis
o Bacteria; gram – diplococcic; 2 million per year
o Polymorphonuclear nuclei; affects women more frequently
o Often has no signs or symptoms but can induce significant inflammatory exudate
o Untreated cases can affect:
 Cervix or fallopian tubes (PID), scarring, infertility
 Prostate gland, seminal vesicles, epididymis
 Triad of arthritis, conjunctivitis, urethritis
 Can infect newborns and cause blindness (trachoma)
o All women <25 should be screened via culture or PCR
o Treatment: antibiotics
 Azithromycin (1 dose), doxycycline (week dose), tetracycline, erythromycin

Question 4

Gonorrhea

Answer 4

– Neisseria gonorrhoeae
o Bacteria; 2nd most common bacterial STI; 0.5 million per year
o Mechanisms: infects the linings of the urethra, genital tract, pharynx, and rectum
o Can cause sterility if untreated
o Diagnosis: culture the exudate  intra- and extracellular gram-negative
o diplococci
o Treatment: antibiotics
 Cephalosporins or (cephtriaxone + azithromycin)

Question 5

Herpes

Answer 5

– 8 virus types
o	Type 1 – oral lesions
o	Type 2 – genital lesions
o	Treatment – no cure and no vaccine;
	Acyclovir, valacyclovir, famciclovir - reduce lesions; interferes w/ viral DNA replication

Question 6

HIV/AIDS Characteristics, Risks

Answer 6

– ENVELOPED virus – instable outside of fluids and cells  low transmission
 50,000 per year
 HIV enters most efficiently via mucous membranes of genitals and anus
 Bind and infect CD4 Helper T cells, macrophages, or dendrites
 Virus replication will begin to destroy helper T-lymphocytes
 Cell immune response becomes compromised  leading to AIDS
o High Risk Behaviors: exchange body fluids; injecting drugs; blood transfusion prior to 1985; maternal-infant (prenatal) transmission

Question 7

HIV/AIDS Infections, Diagnosis, Treatment

Answer 7

o Acute Infection – fever, weight loss, headache, sores, rash, liver/spleen enlargement, nausea, vomiting – “flu like symptoms”
o Chronic Infection – number of opportunistic infections as immune system is compromised (colds, sore throats, fever, tiredness, nausea, night sweats)
o Diagnosis – ELISA test detects HIV antibodies  western blot expensive confirmatory test
o Treatment: new drugs have slowed/blocked progression of HIV  AIDS
 Protease inhibitors block HIV protease enzymes from cleaving precursor proteins to form mature virus proteins
 Antivirals inhibit the HIV reverse transcriptase
 Typically 3-4 drugs taken to inhibit the above
 Stribild (Quad) – incorporates 4 drugs; newer treatment

Question 8

Hepatitis B

Answer 8

– 40,000 per year
o Most infections are acute and self-limited
o Symptoms: nausea, vomiting, aches, pains, decreased appetite, eventually jaundice
o Acute infection determined by detection of HBsAG
o Chronic infection determined by ELISA against surface antigen and inability to clear it
o Progression: acute  chronic  cirrhosis  primary hepatocellular carcinoma (HCC)
 HCC develops after decades of chronic infection
 May involve HVB X protein; constant inflammatory insult and induced cell regeneration
o Treatments: antiviral treatments for chronic disease but NOT curative
 Vaccine against HBV – contains non-infectious HBsAg

Question 9

Syphilis

Answer 9

– Treponema pallidum – bacteria – 15,000 per year
o Progresses in stages
 Primary – development of a chancre that disappears in 3-6 weeks
 Secondary 1to 12 months after chancre disappears, rash/white patches on skin appear
 Latent – infectious lesions, infection can be passed on to fetus
 Late – heart damage, CNS damage, blindness, paralysis, dementia
o Treatment: antibiotics (single penicillin injection)

Question 10

Chancroid

Answer 10

o Bacterial infection with gram negative rod
o Closely mimics syphilis chancres; induces ulcerations causing lymph nodes to become tender
o Mainly in developing countries and in sex workers
o Very rare in US ~50 cases
o Treatment: azithromycin, erythromycin

Question 11

HPV Structure

Answer 11

– MOST COMMON STI
o Virus with NO ENVELOPE – can’t get destroyed by soap/washing
o Protein Shell made up 2 proteins: 95% L1 protein; 5% L2 protein
o 8 kb genome with 7-8 genes
 L1 – makes L1 protein
 L2 – makes L2 protein
 E1 – viral DNA replication and helicase activity
 E2 – transcriptional repressor/activator and works with E1
 E4 – disruption of cytoskeleton
 E5 – mitogenic activity – alters endosomal pH and receptor deactivation)
 E6 and E7 – p53 and pRb degradation - involved in ALL HUMAN CANCERS

Question 12

HPV Types

Answer 12

o Almost 200 types of HPV – 30/40 infect genital tract; 15 associate with cervix;
 HPV1 (feet); HPV2 (hands), HPV4/5/7/8(rare-epidermodysplasia)
 Genital, Anal, and Oral Mucosa – vary histolologically
• Low Risk – 6; 11; 42; 43; 44 – E6 /E7 proteins are different than in high risk
• High Risk – 16; 18; 31; 33; 33; 35; 39; 45; 51; 52; 56; 58; 59; 68

Question 13

Low vs High-risk Characteristics

Answer 13

o Benign epidermal tumors of hands and feet (HPV1; HPV2) – not transferred to genital mucosa
o Benign mucosal tumors (condyloma accuminata, flat genital warts, laryngeal papillomas) – HPV6; HPV11 – do NOT progress to cancers
o Induces Cancers: Cervix, Vagina, Vulva, Penis, Anus, Oropharynx
 Cervical cancers = 2nd most common cause of cancer deaths in women

Question 14

Two Distinct Phases of HPV Life Cycle

Answer 14

o Infect basoepithelial cells  viral assembly  desquamation of cells containing the virus  infection of normal germinal epithelial cells  benign transformation of germinal keratinocytes  formation of papilloma – viral DNA (Episomal)
 Certain PV types involved in progression from episomal to malignancy by integrating into host genome  carcinoma (abnormal cell differentiation)  non productive cells
• Also determined by host genetics, cocarcinogens, immune deficiency

Question 15

Productive Infection

Answer 15

o Viral DNA replicates as episome; both early and late genes expressed
o Abundant capsid proteins synthesize & assemble into infectious virus particle with viral genome
o Pathognomonic changes of “koilocytosis” – representative of acute-infected cells
o Cells induced to form well-differentiated (benign) tumors

Question 16

Malignant Proression

Answer 16

– no viral DNA replication
o Viral genome integrates into host chromsomes
o Integration process “knocks out” viral E2 repressor protein
 resulting in increased E6/E7 expression
o No late genes expressed; no capsid proteins synthesized; no viral assembly
o Lesions have huge nuclei  high nuclear:cytoplasmic ratio

Question 17

Cervical Cancer

Answer 17

– worldwide problem
o 500,000 per year
o Targets transition b/n ecto-cervix (squamous epithelium) to end-cervix (simple columnar)
 Stem-like cells in this region that HPV infects
o 2nd most common cause of cancer death in women
o Takes at least 10 years to progress from productive HPV to pre-cancer stage
 In addition to infection, most need additional genetic events to proceed to malignancy

Question 18

Types of Cervical Intraepithelial Neoplasia & Staging Cancer

Answer 18

– the cancerous tumor condition; CIN I  CIN III

Staging of Cervical Cancer
o 0 = carcinoma in situ (CIN III)
o 4 = extends beyond true pelvis or involves bladder/rectum

Question 19

HPV Diagnosis

Answer 19

o PAP smear combined with biopsy  most common
 Only 50-60% sensitive  partially overcome by frequency of test (once per year)
o Colposcopy – uses a camera to view the cervix with or without acetic acid visualization
 Development of cancer leads to extensive vascularization and engorgement of vessels
o HPV diagnostic tests – tells exactly what type of HPV
 Hybrid capture II assay based on DNA:RNA hybridization-detects multiple types of HPV
• Screens for and differentiated between low and high risk HPV; ~100% sensitivity

Question 20

2 Types of PAP Smear

Answer 20

o Conventional – cervical cell sample manually “smeared” onto slide for screening
 Majority of cells not captured; non-representative transfer of cells; clumping and overlapping of cells; obscuring material  overall not very good
o NEWER - Liquid-based – cervical cell sample put into liquid medium for suspension before automated thin layer/monolayer slide preparation
 Virtually all cells of sample are collected; representative transfer of cells; even distribution of cells; minimizes obscuring; increased sensitivity (80%)  BETTER TEST

Question 21

Therapy of epidermal or external genital HPV infections

Answer 21

– not very specific for HPV strain
o Acids – salicylic or trichloroacetic  most common
o Mitotic inhibitors
o 5-fluorouracil
o Cryotherapy (liquid nitrogen) – freeze thing off
o Excision

Question 22

Therapy of vaginal or cervical HPV Infections

Answer 22

Ablative
 Cryotherapy – freeze entire transformation zone and area of lesion
 Laser Vaporization – vaporize transformation zone containing lesion

Excisional - Conization – cone of tissue is excised for further examination
• Cold Knife Cone – use scalpel
• Laser Conization – use laser
• LEEP (Loop Electrosurgical Excision Procedure) – use thin electric wire loop

Pharmaceutical – used primarily for benign, recurrent lesions – once you stop taking the drug, lesions will return
 Intralesional interferon alpha – lesions recur following withdrawal
 Imiquimod (Aldara) – stimulates host immune response

Question 23

Prevention of cervical HPV infection

Answer 23

o Abstinence
o Condoms
o HPV vaccine – developed at Georgetown

Question 24

HPV vaccine

Answer 24

o Contains a virus-like particle (VLP) made from L1 proteins  induces IgG antibody production against HPV that protects against infection
o Merck – made in yeast with Alum adjuvant; targets HPV6/11/16/18
o GlaxoSmithKline – made in insect cells with AsO4 adjuvant; targets against HPV 16/18

Question 25

Potential Problems with HPV vaccine

Answer 25

– protection by antibodies is TYPE-SPECIFIC
o Almost 200 types of HPVs
o 30-40 infect genital tract
o 12-15 associated with cervical cancer
o Merck vaccine now targets 7 most common HPV types; protects us against 95% infections

Question 26

Artemisinin

Answer 26

– chinese herb and is used to treat malaria currently; may be potential low-cost therapy for cervical cancer