Evaluation of Laboratory Data in Nutrition Assessment

Evaluation of Laboratory Data in Nutrition Assessment
By:Cinda S. Chima, MS, RD

Laboratory Data and the NCP
* Used in nutrition assessment (a clinical sign supporting nutrition diagnosis)
* Used in Monitoring and Evaluation of the patient response to nutritional intervention

Specimen Types
* Serum: the fluid from blood after blood cells and clot removed
* Plasma: fluid from blood centrifuged with anticoagulants
* Erythrocytes: red blood cells
* Leukocytes: white blood cells
* Other tissues: scrapings and biopsy samples
* Urine: random samples or timed collections
* Feces: random samples or timed collections
* Less common: saliva, nails, hair, sweat

Interpretation of Routine Medical Laboratory Tests
* Clinical Chemistry Panels
o Basic metabolic panel
o Comprehensive metabolic panel
* Complete blood count
* Urinalysis
* Hydration status

Clinical Chemistry Panels: Basic Metabolic Panel (BMP)
Also called Chem 7
Includes
o Electrolytes: Na+, K+, Cl-, HCO3 or total CO2
o Glucose
o Creatinine
o BUN
Basic Metabolic Panel Charting Shorthand
Creatinine
CO2
K+
glucose
BUN
Cl
Na
BMP
Clinical Chemistry Panels: Comprehensive Metabolic Panel
Includes
* BMP except CO2
* Albumin
* Serum enzymes (alkaline phosphatase, AST [SGOT], ALT [SGPT]
* Total bilirubin
* Total calcium
Phosphorus, total cholesterol and triglycerides often ordered with the CMP

Clinical Chemistry Panels:
Complete Blood Count (CBC)
* Red blood cells
* Hemoglobin concentration
* Hematocrit
* Mean cell volume (MCV)
* Mean cell hemoglobin (MCH)
* Mean cell hemoglobin concentration (MCHC)
* White blood cell count (WBC)
* Differential: indicates percentages of different kinds of WBC

Clinical Chemistry Panels: Urinalysis
Negative
Leukocyte esterage
Negative
Nitrite
0.1-1 units/dl
Urobilinogen
Not detected
Bilirubin
Negative
Blood
Negative
Ketones
Not detected
Glucose
2-8 mg/dl
Protein
6-8 (normal diet)
pH
1.010-1.025 mg/ml
Specific gravity
Types of Assays
* Static assays: measures the actual level of the nutrient in the specimen (serum iron, white blood cell ascorbic acid)
* Functional Assays: measure a biochemical or physiological activity that depends on the nutrient of interest (serum ferritin, TIBC)
o (Functional assays are not always specific to the nutrient)

Assessment of Nutrient Pool
Assessment of Hydration Status
* Dehydration: a state of negative fluid balance caused by decreased intake, increased losses, or fluid shifts
* Overhydration or edema: increase in extracellular fluid volume; fluid shifts from extracellular compartment to interstitial tissues
o Caused by increase in capillary hydrostatic pressure or permeability
o Decrease in colloid osmotic pressure
o Physical inactivity
* Use laboratory and clinical data to evaluate pt

Hypovolemia
Isotonic fluid loss from the extracellular space caused by
* Fluid loss (bleeding, fistulas, nasogastric drainage, excessive diuresis, vomiting and diarrhea)
* Reduced fluid intake
* Third space fluid shift, when fluid moves out of the intravascular space but not into intracellular space (abdominal cavity, pleural cavity, pericardial sac) caused by increased permeability of the capillary membrane or decrease on plasma colloid osmotic pressure

Symptoms of Hypovolemia
* Orthostatic Hypotension (caused by change in position)
* Central venous and pulmonary pressures 
* Increased heart rate
* Rapid weight loss
* Decreased urinary output
* Patient cool, clammy
* Decreased cardiac output
* Ask the medical team!!
Treatment of Hypovolemia
* Replace lost fluids with fluids of similar concentration
* Restores blood volume and blood pressure
* Usually isotonic fluid like normal saline or lactated Ringer’s solution given IV
* Excess of isotonic fluid (water and sodium) in the extracellular compartment
* Osmolality is usually not affected since fluid and solutes are gained in equal proportion
* Elderly and those with renal and cardiac failure are at risk

Causes of Hypervolemia
* Results from retention or excessive intake of fluid or sodium or shift in fluid from interstitial space into the intravascular space
* Fluid retention: renal failure, CHF, cirrhosis of the liver, corticosteroid therapy, hyperaldosteronism
* Excessive intake: IV replacement tx using normal saline or Lactated Ringer’s, blood or plasma replacement, excessive salt intake
* Fluid shifts into vasculature caused by remobilization of fluids after burn tx, administration of hypertonic fluids, use of colloid oncotic fluids such as albumin

Symptoms of Hypervolemia
* No single diagnostic test, so signs and symptoms are key
* Cardiac output increases
* Pulse rapid and bounding
* BP, CVP, PAP and pulmonary artery wedge pressure rise
* As the heart fails, BP and cardiac output drop
* Distended veins in hands and neck
* Anasarca: severe, generalized edema
* Pitting edema: leaves depression in skin when touched
* Pulmonary edema: crackles on auscultation
* Patient SOB and tachypneic
* Labs: low hematocrit, normal serum sodium, lower K+ and BUN (or if high, may mean renal failure)
* ABG: low O2 level, PaCO2 may be low, causing drop in pH and respiratory alkalosis

Treatment of Hypervolemia
* Restriction of sodium and fluid intake
* Diuretics to promote fluid loss; morphine and nitroglycerine to relieve air hunger and dilate blood vessels; digoxin to strengthen heart
* Hemodialysis or CAVH

Dehydration
* Excessive loss of free water
* Loss of fluids causes an increase in the concentration of solutes in the blood (increased osmolality)
* Water shifts out of the cells into the blood
* Causes: prolonged fever, watery diarrhea, failure to respond to thirst, highly concentrated feedings, including TF

Symptoms of Dehydration
* Thirst
* Fever
* Dry skin and mucus membranes, poor skin turgor, sunken eyeballs
* Decreased urine output
* Increased heart rate with falling blood pressure
* Elevated serum osmolality; elevated serum sodium; high urine specific gravity
* Use hypotonic IV solutions such as D5W
* Offer oral fluids
* Rehydrate gradually

Laboratory Values and Hydration: BUN
Low: inadequate dietary protein, severe liver failure
High: prerenal failure; excessive protein intake, GI bleeding, catabolic state; glucocorticoid therapy
Creatinine will also rise in severe hypovolemia
Decreases
Increases
BUN
Normal: 10-20 mg/dl
Other factors influencing result
Hyper-volemia
Hypo-volemia
Lab Test
Adapted from Charney and Malone. ADA Pocket Guide to Nutrition Assessment, 2004.
Laboratory Values and Hydration Status: BUN:Creatinine Ratio
Low: inadequate dietary protein, severe liver failure
High: prerenal failure; excessive protein intake, GI bleeding, catabolic state; glucocorticoid therapy
Decreases
Increases
BUN: creatinine ratio
Normal: 10-15:1
Other factors influencing result
Hyper-volemia
Hypo-volemia
Lab Test
Laboratory Values and Hydration: HCT
Low: anemia, hemorrhage with subsequent hemodilution (occurring after approximately 12-24 hours)
High: chronic hypoxia (chronic pulmonary disease, living at high altitude, heavy smoking, recent transfusion)
Laboratory Values and Hydration: Alb, Na+
Serum sodium generally reflects fluid status and not sodium balance Serum albumin
Other factors influencing result
Hyper-volemia
Hypo-volemia
Lab Test
Laboratory Values and Hydration Status
Low: diuresis, hyponatremia, sickle cell anemia
High: SIADH, azotemia,
Urine osmolality (200-1200 mosm/kg)
Urine sp. Gravity
1.003-1.030
Serum osmolality
(285-295 mosm/kg)
Other factors influencing result
Serum sodium
Low: malnutrition; acute phase response, liver failure
High: rare except in hemoconcentration
Serum albumin
Other factors influencing result
Hyper-volemia
Hypo-volemia
Lab Test
Hypokalemia (K+< 3.5 mEq/L)
* ↑ renal losses (diuresis)
* ↑ GI losses (diarrhea, vomiting, fistula)
* K+ wasting meds (thiazide and loop diuretics, etc)
* Shift into cells (anabolism, refeeding, correction of glucosuria or DKA)
* Inadequate intake
Hyperkalemia (K+>5.0 mEq/L)
* Decreased renal excretion as in acute or chronic renal failure
* Medications, e.g. potassium sparing diuretics, beta blockers, ACE inhibitors
* Shift out of cells (acidosis, tissue necrosis, GI hemorrhage, hemolysis)

Serum Calcium
* Normal serum 9.0-10.5 mg/dL (includes ionized calcium and calcium bound to protein, primarily albumin, and ions)
* Ionized calcium: 4.5-5.6 mg/dL
* Normal levels maintained by hormonal regulation using skeletal reserves
* Ionized calcium is more accurate, especially in pt with hypoalbuminemia; evaluate before repleting Ca+
Hypocalcemia (serum calcium <9.0 mg/dL; ionized Ca+ <4.5 mg/dL)
* Hypoalbuminemia
* Hypoparathyroidism
* Hypomagnesemia
* Renal failure, renal tubular necrosis
* Vitamin D deficiency or impaired metabolism

Hypercalcemia (serum calcium >10.5 mg/dL; ionized Ca+ >5.6 mg/dL)
* Hyperparathyroidism
* Some malignancies, especially breast, lung, kidney; multiple myeloma, leukemia, lymphoma
* Medications: thiazide diuretics, lithium, vitamin A toxicity
* Immobilization
* Hyperthyroidism
Serum Phosphorus (normal 3.0-4.5 mg/dL)

* Serum phos a poor reflection of body stores because <1% is in ECF
* Bones serve as a reservoir
Hypophosphatemia (<3.0 mg/dL)

* Impaired absorption (diarrhea, Vitamin D deficiency, impaired metabolism)
* Medications: phosphate binding antacids, sucralfate, insulin, steroids)
* Alcoholism, especially during withdrawal
* Intracellular shifts in alkalosis, anabolism, neoplasms
* Refeeding syndrome
* Increased losses: hyperparathyroidism, renal tubular defects, DKA recovery, hypomagnesemia, diuretic phase of ATN




Charney and Malone, 2004, p. 93





Hyperphosphatemia (>4.5 mg/dL)

* Decreased renal excretion: acute or chronic renal failure (GFR<20-25 mL/min); hypoparathyroidism
* Increased cellular release: tissue necrosis, tumor lysis syndrome
* Increased exogenous phosphorus load or absorption, phosphorus containing laxatives or enemas, vitamin D excess
* Acidosis
Hypomagnesemia <1.3 mEq/L (normal 1.3-2.1 mEq/L)
* Decreased absorption: prolonged diarrhea, intestinal or biliary fistula, intestinal resection or bypass, steatorrhea, ulcerative colitis; upper GI fluid loss, gastric suctioning, vomiting
* Renal losses: osmotic diuresis, DM with glucosuria, correction of DKA, renal disease with magnesium wasting, hypophosphatemia, hypercalcemia, hyperthyroidism
* Alcoholism
* Inadequate intake: malnutrition
* Medications
* Intracellular shift: acute pancreatitis
* Refeeding syndrome
Hypermagnesemia (>2.1 mEq/L)
* Acute or chronic renal failure
Assessment for Protein-Calorie Malnutrition
* Hormonal and cell-mediated response
to stress
o Negative acute-phase respondents
o Positive acute-phase respondents
* Nitrogen balance
Assessment for Protein-Calorie Malnutrition–cont’d
* Hepatic transport proteins
o Albumin
o Transferrin
o Prealbumin
o Retinol-binding protein
o C-reactive protein
o Creatinine
* Immunocompetence
Hormonal and Cell-Mediated Response to Inflammatory Stress
* Acute illness or trauma causes inflammatory stress
* Cytokines (interleukin-1, interleukin-6 and tumor necrosis factor) reorient hepatic synthesis of plasma proteins
* Although protein-energy malnutrition can occur simultaneously, interpretation of plasma proteins is problematic

Hormonal and Cell-Mediated Response to Inflammatory Stress
* Negative acute-phase respondents (albumin, transthyretin or prealbumin, transferrin, retinol-binding protein) decrease
* Positive acute-phase reactants (C-reactive protein, orosomucoid, fibrinogen) increase
* The change in these proteins is proportional to the physiological insult

Nitrogen Balance Studies
* Oldest biochemical technique for assessment protein status
* Based on the fact that 16% of protein is nitrogen
* Nitrogen intake is compared to nitrogen output, adjusted for insensible losses (skin, hair loss, sweat)
* Nitrogen balance in healthy adults is 0
* Nitrogen balance is positive in growing children, pregnant women, adults gaining weight or recovering from illness or injury
* Nitrogen balance is negative during starvation, catabolism, PEM
* Nitrogen balance = nitrogen intake (g/24 hours) –(urinary nitrogen [g/24 hours) + 2 g/24 hours
* Use correction of 4 g/24 hours if urinary urea nitrogen is used
* Nitrogen intake = (grams protein/24 hours)/6.25
Nitrogen Balance Challenges
* Urea nitrogen is highly variable as a percent of total nitrogen excreted
* It is nearly impossible to capture an accurate nitrogen intake for patients taking food po
* Most useful in evaluating the appropriateness of defined feedings, e.g. enteral and parenteral feedings

Visceral Proteins:
Serum Albumin
* Reference range: 3.5-5.2 g/dl
* Abundant in serum, stable (half-life 3 weeks)
* Preserved in the presence of starvation (marasmus)
* Negative acute phase reactant (declines with the inflammatory process)
* Large extravascular pool (leaves and returns to the circulation, making levels difficult to interpret)
* Therefore, albumin is a mediocre indicator of nutritional status, but a very good predictor of morbidity and mortality
Visceral Proteins: Plasma Transferrin

* Reference range: 200-400 mg/dl
* Half-life: 1 week
* Negative acute phase respondent
* Increases when iron stores are depleted so affected by iron status as well as protein-energy status
* Responds too slowly to be useful in an acute setting
Visceral Proteins: Transthyretin (Prealbumin)
* Reference range: 19-43 mg/dl
* Half-life: 2 days
* Negative acute-phase reactant
* Zinc deficiency reduces levels
* Due to short half-life, it is useful in monitoring improvements in protein-energy status if baseline value is obtained near the nadir as inflammatory response wanes
Visceral Proteins: Retinol-Binding Protein
* Reference range: 2.1-6.4 mg/dl
* Half-life: 12 hours
* Negative acute-phase protein
* Unreliable when vitamin A (retinol) status is compromised
* Elevated in the presence of renal failure, regardless of PEM status

Visceral Proteins: C-Reactive Protein
* Positive acute-phase reactant
* Increases within 4-6 hours of injury or illness
* Can be used to monitor the progress of the stress reaction so aggressive nutrition support can be implemented when reaction is subsiding
* Mildly elevated CRP may be a marker for increased risk for cardiovascular disease
Inflammation
* hs-CRP
* Homocysteine

Urinary Creatinine
* Formed from creatine, produced in muscle tissue
* The body’s muscle protein pool is directly proportional to creatinine excretion
* Skeletal muscle mass (kg) = 4.1 = 18.9 x 24-hour creatinine excretion (g/day)
* Confounded by meat in diet
* Requires 24-hour urine collection, which is difficult
Markers of Malabsorption
* Fecal fat
* Fat-soluble vitamins
* Vitamin D
Lipid Indices of Cardiovascular Risk
* Total cholesterol
* LDL
* HDL: HDL2a, HDL2b, HDL2c, HDL3a, HDLdb
* IDL
* VLDL
* Lp(a)
Nutrition Diagnoses and Laboratory Indices
* Nutrition-related labs can be used either as diagnostic labels or a clinical sign
Examples of Nutrition Diagnostic Statements Related to Lab Values
* Altered nutrition-related lab values (NC-2.2) related to excessive intake of saturated fat and cholesterol and genetic factors as evidenced by diet history and client history.
* Inappropriate intake of food fats (saturated fat and cholesterol) (NI-5.6.3) related to frequent use of baked goods and fried foods as evidenced by diet history and elevated LDL and TC
Examples of Nutrition Diagnostic Statements Related to Lab Values

* Excessive carbohydrate intake related to evening visits to Coldstone Creamery as evidenced by HS blood glucose and diet history

Evaluation of Laboratory Data in Nutrition Assessment.ppt

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HIV/AIDS 2008 Update

HIV/AIDS 2008 Update
By:David H. Spach, MD
Clinical Director, NWAETC
Professor of Medicine
Division of Infectious Diseases
University of Washington, Seattle

* HIV Epidemiology
* HIV Rapid Testing
* 2008 DHHS ARV Therapy Guidelines
* Antiretroviral Therapy: New Information in 2008
* New Scientific Discoveries
DHS/PP
Epidemiology*
Question
* In August 2008, the CDC reported their use of new epidemiologic methods that has led to significant revisions in the estimates of HIV incidence in the United States.

DHS/PP
In this recent report, which one of the following statements is TRUE regarding HIV infections in the United States in 2006?

* The number of estimated new infections in 2006 has been revised to a lower number (now 32,000 instead of 40,000)
* The rate (per 100,000 persons) of new infections in blacks was 7x whites
* Heterosexual sex has replaced male-to-male sex as the leading transmission category for new infections
* The number of new infections in women was greater than men
* “Based on extrapolations from these data, the estimated number of new infections for the United States in 2006 was 56,300.”
* “... the level of new HIV infections in the United States is higher than had previously been known, in fact approximately 40% higher than early estimates…”
Kevin Fenton, MD, PhD
Centers for Disease Control & Prevention.
HIV Rapid Testing*
Rapid HIV Tests
* In the June 18, 2008 issue of the MMWR, the NY City Department of Health and the CDC reported a problem with the OraQuick ADVANCE Rapid HIV-1/2 Antibody Test.

What was the reported problem with the OraQuick rapid HIV test?
* Contamination of test kits with mold
* Kits were shipped too close to the expiration date
* Failure of external Kit Controls to validate the assay
* Increased numbers of False-Positive results with oral fluid samples

Persons NOT Infected with HIV
OraQuick Rapid ORAL HIV Test
Confirmatory HIV Test (EIA/WB)
Preliminary
Positive
EIA
WB
Reactive
Oral Fluid
Oral
Possible Revised Approach: Rapid HIV Testing
OraQuick Rapid HIV Tests
Confirmatory HIV Test (EIA & WB)
Preliminary
Positive
Reactive
Oral
Oral Fluid
EXAMPLE: Specificity of HIV Antibody Test
Persons NOT Infected with HIV (N = 15)
EXAMPLE: Specificity of HIV Antibody Test
Antibody Test Result: Persons NOT Infected with HIV
EXAMPLE: Specificity of HIV Antibody Test
HIV Antibody Testing in Low Prevalence Setting
HIV Test Specificity
HIV Antibody Testing in Low Prevalence Setting
DHHS ARV Guidelines
Initiating Antiretroviral Therapy
* As a group, make a list of at least 5 recommendations regarding initiating antiretroviral therapy that are new/different in current 2008 guidelines when compared with guidelines that existed one year ago at this time (at that time October 2006 most recent updated version).
Initiating Antiretroviral Therapy
* NEW RECOMMENDATIONS
1. New CD4 threshold (350 cells/mm3 in 2008 instead of 200)
2. New indications for starting ARV (chronic HBV, HIVAN) in 2008
3. Less impact of HIV RNA level in 2008
4. Zidovudine-lamivudine removed from preferred list in 2008
5. Abacavir-lamivudine added to preferred list in 2008
6. Do HLA-B5701 testing if considering using abacavir
Initiating Antiretroviral Therapy January 2008 DHHS Guidelines
*Initiate Antiretroviral Therapy
Consider Antiretroviral Therapy
Construct Regimen by choosing one component from Column A and one component from Column B
Recent Concerns Regarding Abacavir
Antiretroviral Therapy New Information in 2008
Host Cellular Receptors
Extracellular Space
Intracellular Space
Entry Inhibitor: Maraviroc (Selzentry)
Host Cell Membrane
CD4 Receptor
Extracellular Space
Intracellular Space
R5 HIV
Maraviroc
CXCR4
CCR5
HIV Co-Receptor Tropism Assay Monogram Biosciences Trofile Assay
HIV-1 Tropism Assay
What is the major difference in the new ENHANCED Trofile assay when compared with the older Trofile assay?

* The new assay has a lower limit of detection of minor species (<1% compared with previous lower limit of 10%)
* Results can be obtained in 7 days with the new assay
* The new assay is accurate with very low HIV RNA levels (accurate down to 100 copies/ml)
* The new assay detects CCR5 mutants resistant to Maraviroc

HIV Co-Receptor Tropism Assay Monogram Biosciences ENHANCED Trofile Assay
Tenofovir + Lamivudine + Efavirenz (n = 38)
Eligibility
- HIV-infected
- Treatment Naive
- HIV RNA > 5,000 copies/ml
- CD4 count > 100 cells/mm3
- Randomized, double-blind
Tenofovir + Lamivudine +
Raltegravir* (n = 160)
Virologic Response: Week 24
INVESTIGATIONAL
* Background
- N = 368
- ARV-naīve
- HIV RNA > 5,000 copies/ml
- Randomized, double-blind
* Regimens (all include 2 NRTIs*)
- Efavirenz: 600 mg qd
- Rilpivirine: 25 mg qd
- Rilpivirine: 75 mg qd
- Rilpivirine: 150 mg qd
New Scientific Discoveries
A Cure for HIV?
* In July 2008, our patients starting coming in asking about the news reports regarding the newly discovered cure for HIV. The report that came out in July 2008 was related to HIV gp120 (envelope).

What new therapeutic strategy was discovered?

* A CD4 coating molecule that is an inhibitor of gp120-CD4 binding
* Use of Abzymes to destroy a critical region of gp120
* A new enzyme that cause gp120 to separate from gp41
* A new particle that destroys the human co-receptor CCR5 and thus prevents gp120-CCR5 binding

HIV: Basic Structure
DHS/PP
gp120
gp41
Envelope
HIV: Envelope
Abzymes
- Antibodies with enzymatic activity
- Can break down thousands of virus particles per molecule of abzyme

HIV: gp120
DHS/PP
HIV gp120: Abzyme Interaction .........

HIV/AIDS 2008 Update: Summary

* HIV Epidemiology
* HIV Rapid Testing
* 2008 DHHS ARV Therapy Guidelines
* Antiretroviral Therapy: New Information in 2008
* New Scientific Discoveries

HIV/AIDS 2008 Update.ppt

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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

Update on Infections .ppt

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