Update on Infections

Update on Infections
By:Mark A. Lassoff, MD, MBA, MPH
September 18, 2007

Malacoplakia
* “malako” – soft, “plakos” – plaque
* Rare granulomatous disease
* Michaelis – Gutmann bodies: basophilic lamellar inclusion bodies
* Associated with other autoimmune diseases
o Sarcoidosis, Chedak-Higashi syndrome
* Incidence: 1 in 10,000
* Female: Male – 4:1
* Peak incidence is in patients ≥ 50 yrs old
* 75% of cases occur in GU system, most commonly in the bladder (2nd – kidney)
* Predilection for those with immunodeficiency, systemic dz, carcinoma or chronic UTI with coliform organisms (E Coli – up to 75%, Enterobacter, Klebsiella, Proteus and Pseudomonas)
* Etiology – unknown
o Theory: acquired immunodeficiency interfering with normal intracellular function of the monocyte’s phagolysosome. Residual undigested bacterial components become mineralized by Ca++ & Fe
o Cause appears to be related to imbalance in the intracellular cGMP/cAMP
* Dx made by biopsy
o Lesion: large histiocytes  von Hansemann cells and small intracytoplasmic calculospherules  Michaelis-Gutmann bodies
o Immunohistochemical staining for α1-antitrypsin useful for early and accurate differential dx
* Clinical findings
o Bladder
+ Irritability and hematuria
+ Mucosal plaques or nodules  fungating, firm, sessile masses
o Renal
+ Bilaterality in up to 50%; multifocal is more common
+ Fever, flank pain or mass on PE
+ Cause loss of function via direct invasion or obstruction
+ E Coli infxn in up to 93%
+ Bilateral dz  mortality rate approaches 100% w/i 6 mos of dx w/o intervention
+ IVP: unifocal – may displace calyces vs. multifocal – nephromegaly and poor renal fxn; multiple filling defects
* Management
o Lower tract:
+ Initial treatment with medications
# Bethanecol (↑ cGMP), Ascorbic acid (↓ cAMP)
# Fluoroquinolones (DOC)
# Others: Bactrim, Rifampin, Cipro
+ TUR prn for plaque removal
o Upper tract:
+ Unilateral renal dz: most often requires nephrectomy
o In immunodeficient pts and those with multifocal dz, surgical tx is essential to survival

Sexually Transmitted Infections
Syphilis
* Treponema pallidum (spirochete)
* Spread: infectious lesions, body fluids, in utero, blood transfusions
* Primary
o Single painless, indurated ulcer appearing 3 wks after inoculation (@ site of inoculation) and remains for 4 – 6 wks
o Often with bilateral, non-tender inguinal or regional lymphadenopathy
o Can heal w/o treatment; often goes unnoticed
o Presence of chancres increases risk of HIV acquisition 2-5x
* Latent
o Seroreactivity w/o clinical evidence of dz
o Early: within the last year
o Late latent vs. latent syphilis of unknown duration
* Secondary
o Begins 4 – 10 wks after the appearance of the ulcer but may present up to 24 mos after initial infection
o Mucocutaneous, constitutional and parenchymal signs and symptoms
+ Maculopapular rash (trunk and arms)
+ Generalized non-tender lymphadenopathy
+ Papular rash (may accompany first rash)
# Becomes necrotic and pustular
# Affects palms and soles
# Intertriginous areas: enlarge and erode  condyloma lata (infectious)
+ Less commonly: hepatitis and immune-complexed glomerulonephritis
* Tertiary
o One third of untreated pts
o Rare in industrialized countries, except for pts w/ HIV
o Cardiovascular, skeletal, CNS, skin
+ Aortitis, meningitis, uveitis, optic neuritis, general paresis, tabe dorsalis, gummas of skin/skeleton
* Screening
o Rapid Plasma Reagin (RPR) & Venereal Disease Research Laboratory (VDRL)
+ Correlate with disease activity
+ Become negative one year after treatment
o T. pallidum particle agglutination (TP-PA) or Fluorescent Treponemal Antibody Absorbed (FTA-ABS)
+ Antibody tests remain positive for life; do not correlate w/ active disease
o HIV can cause FN results by treponemal & non-treponemal methods
* Treatment
o Benzthiazide penicillin G (2.4 million units IM x 1)
o Jarisch – Herxheimer rxn
+ Headaches, myalgia, fever, tachycardia, increased resp rate within first 24 hrs after tx w/ PCN
+ Managed with bed rest and NSAIDs
o PCN allergy: Doxycycline (100mg BID x 14d)
o Latent: PCN IM weekly x 3 doses or doxycycline for a total of 4 wks
o Tertiary: Aqueous crystalline PCN G (IV q4h) x 10-14 d or PCN G procaine IM + probenecid (po QID) x 10-14 d
o Pregnancy: desensitization to PCN

Herpes Simplex Virus
* Genital herpes: HSV-2 (85-90%), HSV-1 (10-15%)
* Silent infection may account for >75% of transmission
* Primary
o Painful ulcers of genitalia or anus
+ Group of vesicles on an erythematous base that does not follow a neural distribution is pathognomonic
o Bilateral painful inguinal adenopathy
o Often associated with constitutional flu-like symptoms
o Urethral lesions may cause transient urinary retention in women
o Asx viral shedding can happen up to 3 mos after clinical presentation
* Recurrent episodes are usually less severe
* Severe dz and complications:
o Pneumonitis, disseminated infxn, hepatitis, meningitis, encephalitis
* Dx: viral culture with subtyping (gold standard)
o Not on clinical suspicion alone, classic presentation occurs in a small percentage of pts
o Can see abrasions, fissures or itching
o Subtyping is important for prognosis and counseling
+ HSV-2: ave of 4 recurrences in 1st yr vs. 1 for HSV-1
o Sensitivity: 30 – 95% depending on stage of lesion and whether it is primary or recurrence
* Treatment
o Oral acyclovir, valacyclovir and famciclovir
o Topical meds are not effective
o Recurrences: episodic or suppressive approach
+ Suppressive: decreases frequency/duration and viral shedding
Chancroid
* Haemophilus ducreyi
* Men: Women – 3:1
* Painful, non-indurated ulcer on penis or vulvovaginal area
o Friable base covered with a gray or yellow purulent exudate and a shaggy border
* Inguinal adenopathy is typically unilateral and tender with tendency to become suppurative and fistulize
* Dx: culture media not widely available so gram stain often helpful (short, fine, GN streptobacilli in short, parallel chains)
* Approximately 10% are co-infected w/ HSV or syphilis
* Treatment
o Single dose
+ Azithromycin 1gm po or Ceftriaxone 250mg IM
o Other tx: Cipro x 3d or Erythromycin x 7d

Lymphogranuloma Venereum
* Chlamydia trachomatis – L1, L2, L3
* Single, painless ulcer on the penis, anus or vulvovaginal area that goes unnoticed
* Painful unilateral suppurative inguinal adenopathy and constitutional symptoms that occur 2 – 6 wks after resolution of ulcer
* Significant tissue injury and scarring can occur leading to labial fenestration, urethral destruction, anorectal fistulas and elephantiasis of penis, scrotum or labia
* Dx: mainly clinical
o Complement fixation or indirect fluorescence antibody titers can confirm
* Tx: Doxycycline BID or erythromycin QID x 3 wks

Genital Warts
* Condylomata acuminata
* Human papillomavirus (HPV) – DNA virus
* Types 6 and 11 are most often responsible for visible external genital warts
o Cervix, vagina, urethra, anus, mucous membranes
* Types 16, 18, 31, 33, 35, 39, 45 and 51: associated with cervical dysplasia and neoplasm in women and squamous intraepithelial neoplasia in men
o >99% of cervical cancers and 84% of anal cancers are associated with HPV (16 & 18)
o Cervical cancer is considered an AIDS defining illness
* Most are subclinical and asx
* In women HPV may be associated with nonspecific symptoms such as vulvodynia or pruritis; malodorous vaginal discharge
* Dx: usually inspection or palpation
* Bx: not routinely needed
o Atypical, pigmented, indurated, fixed or ulcerated
o Lesions persist/worsen after tx; immunocompromised pts
* Treatment
o Depends on size, number, location, and patient and physician preference
o Observation (spontaneously resolve with time)
o Patient applied (less expensive)
+ Podofilox 0.5% solution or gel (3d on, 4d off, may repeat x 4)
+ Imiquod 5% cream (3/wk qhs for up to 16 wks)
# Needs to be washed off, can cause ulceration
o Provider applied
+ Cryotherapy with liquid nitrogen
+ Electrosurgery
+ Laser therapy (CO2)
+ Podophyllin resin (20 – 25%)
+ Trichloracetic acid (TCA) or bichloracetic acid (BCA)
+ Surgical excision
* Lesions around the meatus may herald presence of urethral or bladder condyloma
* Urethral or bladder lesions should be cystoscopically excised
* Intraurethral 5% FU cream 2/wk
* Vaccine containing 8 of the most common HPV types associated with cancer could potentially prevent 95% of cervical cancer
* Topical BCG: promising preliminary results

Sexually Transmitted Infections
Chlamydia
* Chlamydia trachomatis: most common bacterial STD in the US and worldwide
* Majority of men and women are asx
* 50% of men experience LUTS attributed to urethritis, epididymitis or prostatitis; may see clear or white urethral discharge
* 75% of women are asx and 40% of those untreated will have PID
* May be transmitted during vaginal birth
o Ocular, oropharyngeal, respiratory, urogenital or rectal infxn
Chlamydia
* Women should be screened annually until 25 yo or if risk factors such as new sexual partner are present
o Nucleic acid amplification test (NAAT) on endocervical swab or urine specimen
o Unamplified nucleic acid hybridization test, enzyme immunoassay or direct fluorescence antibody test
o Culture
* Treatment
o Azithromycin 1gm po x 1 or Doxy BID x 7d
o Refrain from sex until treatment completed or 7d after single dose therapy
o Re-culture recommended 3 wks later if treated with erythromycin, in pregnant women or if symptoms persist
o Re-screened 3 – 4 mos after tx as are high risk for re-infxn

Gonorrhea
* Neisseria gonorrhoeae (GN diplococcus)
* Men usually experience LUTS attributed to urethritis, epididymitis, proctitis or prostatitis w/ associated mucopurulent urethral discharge
* Women may have vaginal and pelvic discomfort, dysuria or abnormal vaginal discharge but are usually asx
* Same screening recs as for Chlamydia
* Treatment
o Ceftriaxone 125mg IM x 1
o Single dose oral regimen
+ Cipro, Levaquin, Ofloxacin (growing resistance to FQs)
o Simultaneous treatment for Chlamydia






Trichomoniasis

* Trichomonas vaginalis (flagellated protozoan)
* Increased incidence in developing countries and those with multiple sexual partners
* Can inhabit the vagina, urethra, Bartholin glands, Skene’s glands and prostate (not rectum/mouth)
* Men: usually asx but can produce short-term urethral discharge, dysuria and urgency
* Women: asx in 50%, otherwise can see sudden onset of frothy white or green, foul-smelling vaginal discharge, pruritis, and erythema
o Dyspareunia, suprapubic discomfort, urgency
Trichomoniasis
* Examination: frothy discharge and “strawberry vulva” or “strawberry cervix”
* Vaginal discharge has increased pH
* Motile protozoa on vaginal wet-mount smear or microscopic examination of urine
* Men: urethral cx or microscopic exam of urine
* Treatment
o Metronidazole 2gm po x 1 (ok in 2nd trimester)
+ GI side effects common
o Abstain from Etoh consumption
o Prolonged Metronidazole for failure

Vaginitides / Urethritides
* Ureaplasma urealyticum, Mycoplasma hominis, Mycoplasma genitalium
o Implicated in chronic prostatitis and urgency frequency symptoms in women and in up to 40% of NGU
o Tx: Azithromycin po x 1 or doxycycline x 2 wks
* Bacterial vaginosis
o Gardnerella vaginalis, anaerobic orgs, Mycoplasma and/or inhibition of normal vaginal flora
o 10% KOH with vag secretions  fishy odor secondary to release of amines
o Microscopic exam (3 of 4 necessary): (1) thin, white vag d/c (2) vag pH >4.5 (3) clue cells (4) pos whiff test
o Tx: Metro po BID x 7d, Clinda cream x 7d, Metro gel x 5d
* Candida albicans
o Thick, cheesy vaginal discharge usually associated with vulvar irritation and itching
+ Vaginal discomfort, burning, dyspareunia and external dysuria
o Dx: yeast or pseudohyphae on wet prep or gram stain
o Tx: single oral dose of fluconazole (150mg) or OTC antifungal vaginal creams, tablets or suppositories x 1-7 days (butoconazole, clotrimazole, miconazole and terconazole)
References

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HUMAN PAPILLOMA VIRUS (HPV)

HUMAN PAPILLOMA VIRUS (HPV)
By: Nathalia Cruz

What is a Virus?
* Exceptionally simple living microbes.
* Contain a single type of nucleic acid (DNA or RNA) and a protein coat.
* Obligatory intracellular parasites.
* Range from 20 to 14.000 nm in length.
* It’s classification is based on type of nucleic acid, strategy for replication, and morphology

HUMAN PAPILLOMA VIRUS
* HPV is the virus that causes warts.
* More than 100 different kinds, 30-some of this cause genital HPV.
* Spread by sexual contact or from mother to baby.
* Genital warts appear 6 weeks to 8 months after contact with an HPV infected person.
* The most common sexually transmitted disease worldwide.
* Certain types of HPV are linked with cervical cancer.
* Divided into 2 subcategories: Genital Warts and Cervical Dysplasia.
* Most people do not know they have it.
* There are high risk and low risk types of it.

HISTORY
* The papillomaviruses are part of the PAPOVAVIRIDAE family of DNA tumor viruses.
* First discovered in the early 40’s.
* Gained notoriety in the early 80’s when it was discovered that some types of HPV caused cervical cancer.

MORPHOLOGY
* Papilloma virus genome is circular covalently closed double stranded DNA of about 8 kbp.
* All PV genes are coded in one of the 2 DNA strands utilizing the alternative splicing for the individual expression of each gene.
* Papillomavirus expression is characterized by a large array of mRNAs cells coding for different genes.
* 55 nm in diameter.

MECHANISM OF INFECTION
* All PV exhibit extreme specificity for infection on epithelial cells.
* The papillomavirus epitheliotrophy resides in the interaction of specific transmission factors with the viral regulatory region LCR.
* The infection normally results in hyperproliferation of the host cell and may lead to transformation and immortalization.

GENITAL WARTS
* Sometimes called condylomata acuminata.
* Are soft, moist or flesh colored, and appear in the genital area within weeks or months after infection.
* Sometimes appear in clusters and are either raised or flat, small or large.
* Women: appear in the vulva, cervix, vagina and anus.
* Men: Can appear on the scrotum or penis.

LIFE CYCLE (HPV-16)
* Starts with the infection of the host cell.
* The virus DNA is released within the nucleus
* Numerous cellular transcription factors interact with the non-coding viral regulatory region (LCR), starting transcription of the two hpv-16 transforming early genes (E6 and E7).
* The transforming proteins interact with the cellular antioncogenic regulator p53 disrupting the cell cycle.

HPV TYPES
* Numbered in order of discovery.
* 30 HPV types primarily infect the squamous epithelium of the lower anogenital tracts of both males and females.
* HPV types 6, 11, 42, 43, or 44 present as papillary condylomas, may also present as flat lesions that may or may not be visible to the unaided eye are part of the “low-risk” HPV types.
* Types 16, 18, 31, 33, 35, 45, 51, 52, and 56 are considered “high-risk” types because they have been found in cervical and other lower genital tract cancers.

HPV GENOMIC ORGANIZATION
* Three main regions (early, late and the long control region)
* (E) resides the transformation and immortalization potential.
* (L) Two capsid genes.
* (LCR) contains all the cis-regulatory elements.

HOW HPV CAUSES CANCER
* HPV DNA integrates into the host genome.
* The proteins E6 and E7 are produced from the resultant DNA.
* E6 binds and degrades p53 (a tumor suppressor gene).
* If the DNA is altered, the cell keeps replicating. The mutation rate of the cell increases.
* E7 binds and degrades retinoblastoma (another tumor suppressor gene).
* Retinoblastoma normally keeps the cell from growing too fast or responding to growth stimulators. This inhibitory factor is now lost.
* without these two mechanisms to slow down cell growth and prevent mutation. . .
* Malignant Transformation Occurs.

HPV TREATMENT
* Genital warts can be treated by a doctor and by different methods.
* Podofilox gel: A patient-applied treatment for external genital warts.
* Imiquimod cream: A patient-applied treatment.
* Chemical treatments (including trichloracetic acid and podophyllin), which must be applied by a trained health care provider to destroy warts.
* Cryotherapy: Uses liquid nitrogen to freeze off the warts.
* Laser therapy: Uses a laser beam or intense lights to destroy the warts.
* Electrosurgery: Uses and electric current to burn off the warts.
* Surgery: Can cut away the wart in one office visit .
* Interferon: an antiviral drug, which can be injected directly into warts.

CURE
* There is currently no cure for human papillomavirus.
* Once an individual is infected, he or she carries the virus for life even if genital warts are removed.
* The development of a vaccine against HPV is under way, but is still not available.
* If left untreated, some genital warts may regress on their own.

HUMAN PAPILLOMA VIRUS.ppt

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Protect yourself and Protect others! During this Flu Season

Protect yourself and Protect others!
During this Flu Season…

This module has been designed to provide information to the Duke Employees on seasonal and H1N1 Flu. After completing this module, you will be able to:

* Identify important facts related to seasonal and H1N1 Flu
* Describe proper hygiene practices and control measures, including vaccination to prevent
o Seasonal Flu and
o H1N1 Flu

* Describe the impact of the seasonal flu and H1N1Flu on employees and on Duke as an organization

Why Should I Be Concerned?

+ Typically, the” Flu” comes around yearly during the fall and early winter. This is considered the “seasonal” Flu and a vaccine is developed each year to provide protection against the most common strains that are expected to cause the most illness.
* Seasonal Flu is a serious disease. In fact, 25,000 to 35,000 die annually in the U.S. due to the seasonal Flu. Those at the highest risk for developing complications are:
o The elderly
o The very young
o Those with chronic medical conditions, such as heart disease, lung disease, diabetes or conditions that effect the immune system

Why Is This Year’s Flu Season Different?

+ This year, there is a new and very different Flu virus spreading worldwide called the H1N1 Flu or formerly known as the “Swine Flu”. Though this new type of Flu is turning out to be milder than originally feared, it can lead to complications.
+ At this time, many are susceptible to the H1N1 and those infected experience symptoms similar to the seasonal Flu. Those at highest risk for complications seem to be:
# Pregnant women
# Children
# Youth and young adults up to age 24
# Those with chronic medical conditions between ages 24 and 64

What Does This Mean For DU/DUHS?

Based on the government’s current estimate, 30-50% of our employees could be infected with the Flu this season.

Since we work closely together in the Duke community, we have many opportunities for contact.

Duke is taking steps to slow the spread of illness in the workforce.

Protecting yourself, your co-workers and your patients is the best way to decrease the impact of either the seasonal Flu or the H1N1 Flu. You’ll find out how in the next slides.


Remember that we all are susceptible to BOTH kinds of Flu.

To Protect Yourself & Prevent Spread . . .

It is important to know that the Flu is highly contagious, and spreads when the virus is passed from one individual to another individual. This can happen when an infected individual:

o Coughs, sneezes, or has direct physical contact with another individual
o Indirectly contaminates objects such as door knobs, telephones or surfaces. This is not the most common route of infection.

Remember that the virus can spread from the hands to eyes, nose, and mouth; so good hand hygiene is critical.

Here’s What You Can Do To Prevent Spreading The Virus . . .

+ Wash your hands. Washing hands often with soap and water or an alcohol-based hand cleaner will help protect against germs.
+ Cover your nose and mouth with a tissue when you cough or sneeze. Throw the tissue in the trash immediately after use. Wash your hands immediately.
+ If a tissue is not available, cough or sneeze into your elbow or sleeve.
+ Avoid touching eyes, nose or mouth. Germs are often spread when you touch something contaminated with germs and then touch your eyes, nose or mouth.
+ Stay home and away from others when you’re sick. You will help prevent others from getting sick.

And Take The Time To Get Vaccinated

* Too many employees unwisely continue to work while sick with the Flu.
* Unvaccinated workers who are not yet feeling sick can spread the virus.
* Infected individuals may be infectious the day before they become sick as well as after their fever is gone.

YOU maybe the source of Flu transmission!

Get Vaccinated for Seasonal Flu
The Center for Disease Control recommends a seasonal flu vaccine as the first and foremost important step in protecting against seasonal flu. Vaccination for seasonal Flu is vital for:

* Individuals at high-risk for serious Flu complications:
o The elderly
o The very young
o Those with chronic medical conditions, such as heart disease, lung disease, diabetes or conditions that effect the immune system
* Health care workers
* Individuals who live with or care for high-risk individuals
* All persons wishing to prevent seasonal flu


For more information, go to www.cdc.gov
Remember That DU/DUHS Offers Free
Seasonal Flu Vaccination

* Duke offers free seasonal flu vaccination to all employees.
* Times and locations of flu vaccination sites will be posted online at www.duke.edu/flu.
* Bring your Duke ID to receive the vaccination.
* If you have a fever, postpone your flu shot.

And Remember To Get Vaccinated for H1N1

* The seasonal Flu vaccine will not protect you against the H1N1 Flu.
* A separate vaccine is being developed for H1N1. It is expected to be available in late fall.
* The H1N1 vaccine will be distributed based on criteria as defined by the Centers for Disease Control (CDC).

How Do I Know If I Have The Flu?

Symptoms for both the Seasonal Flu and H1N1 Flu are similar . . .

o Fever of 100 degrees or more and any of these symptoms:
+ Cough
+ Sore throat
+ Runny or stuffy nose/sneezing
+ Body ache
+ Headache
+ Chills
+ Unusual fatigue

How Should I Care for Myself?

* Get Extra Rest
* Increase Fluid Intake
* Take Fever Lowering Medication (no aspirin for children)
* If you have severe illness or you are at high risk for flu complications, contact your health care provider or seek medical care.

Seek Urgent Medical Attention If You Experience . . .

Any of these emergency warning signs . . .

* Difficulty breathing or shortness of breath
* Pain or pressure in the chest or abdomen
* Sudden dizziness
* Confusion
* Severe or persistent vomiting

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