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Title: EmergingReemerging Diseases: Update 2003


1
Emerging/Reemerging DiseasesUpdate 2003
  • Louis G. DePaola, DDS, MS

Professor Department of Diagnostic
Sciences and Pathology Dental School
University of Maryland Baltimore

2
Emerging Infectious Diseases/Agents
in the USA, 2003
  • Chlamydia
  • Diphtheria
  • Encephalitis
  • West Nile
  • St. Louis
  • E. coli
  • N gonorrhea
  • H. Influenzae
  • Hantavirus
  • Hepatitis A-G
  • Human herpes viruses
  • HHV 1-8
  • HIV/AIDS
  • Human papilloma viruses
  • Influenza
  • Emerging strains
  • Legionella pneumophila
  • Lyme Disease

3
Emerging Infectious Diseases/Agents
in the USA, 2003
  • Measles
  • Meningococcus
  • MRSA/VRSA
  • Pertussis
  • Poliomyelitis
  • Rabies
  • Rocky Mt.
    Spotted Fever
  • Rubella
  • SARS
  • Severe Acute Respiratory Syn
  • Salmonellosis
  • Shigellosis
  • S. pneumoniae
  • Syphilis
  • Tetanus
  • Toxic-Shock Syndrome
  • Tuberculosis

4
VaccinationsPrevent Disease
5
Immunization Programs
  • National guidelines for immunization of, and PEP
    for, HCP, which includes DHCP, are provided by
    the US Public Health Services Advisory Committee
    on Immunization Practices
  • ACIP, CDC/ACIP 1997 and 2001
  • Based on studies of health-care infections,
    susceptible HCP are
    considered to be at occupational risk for
    acquiring
  • HBV or HCV infection,
  • And at risk for acquiring or transmitting
    influenza, measles, mumps, rubella, and chicken
    pox (varicella).
  • The ACIP recommends that all HCP be vaccinated or
    have documented immunity to all
    vaccine-preventable diseases
  • HBV
  • Influenza
  • MMR
  • Varicella

DRAFT
6
Immunization Programs
  • Immunizations are an essential part of prevention
    and infection control programs for DHCP and
    dental health-care facilities are encouraged to
    formulate a comprehensive immunization policy.
  • These policies should include a checklist of
    required and recommended vaccinations for
    specific job categories, including

DRAFT
7
Immunization Programs
  • Appropriate vaccination and booster schedules
  • Determination of the immune status
    of newly hired employees
  • And considerations for DHCP unable
    or unwilling to be vaccinated as required or
    recommended.
  • Policies also should reflect the regulations and
    recommendations on the vaccination of HCP
    established by individual states and professional
    organizations

DRAFT
8
Vaccine Preventable Diseases Adults
  • Diphtheria
  • Hepatitis A
  • Hepatitis B
  • Influenza
  • Lyme Disease
  • Measles
  • Haemophilis influenza type B (Hib)
  • Mumps
  • Pneumococcus
  • Polio
  • Rubella
  • Tetanus
  • Varicella

May not be needed if certain conditions are met

Very important in adults over 65
www.cdc.gov, 2/4/2002
9
Vaccination of Pregnant Women
  • Risks are largely theoretical
  • Generally live-virus vaccines contraindicated
  • Benefit of vaccination outweighs risk if
  • Risk for exposure to disease is high
  • Infection poses a risk to fetus
  • Vaccine is unlikely to cause harm
  • Acceptable
  • Hepatitis B
  • Influenza
  • Tetanus/Diphteria
  • Meningococcus
  • Rabies
  • Contraindicated
  • Measles
  • Mumps
  • Rubella
  • Varicella
  • BCG
  • Vaccinia

National Immunization Program www.cdc.gov/nip
10
Vaccine Preventable DiseasesChildren
  • Diphtheria
  • Hepatitis A
  • Hepatitis B
  • Pertussis
  • Measles
  • Haemophilis influenza type B (Hib)
  • Mumps
  • Polio
  • Rubella
  • Tetanus
  • Varicella


www.cdc.gov, 02/02
Single vaccine - MMR
11
Rubella
  • Respiratory transmission of the virus
  • Highly contagious Incubation 12-23 days
  • Replication in nasopharynx/lymph nodes
  • Viremia 5-7 days post-exposure
  • Placenta and fetus infected during viremia
  • Rash, low grade fever, malaise, adenopathy
  • Fainter rash than measles and non-coalescent
  • Disastrous disease in early gestation
  • Infection at
  • Causes Congenital Rubella Syndrome
  • Multiple organ damage death
  • Prevention paramount!!!
  • Vaccination MMR

National Immunization Program www.cdc.gov/nip
12
(No Transcript)
13
MMR Vaccine Not Associated With
Increased Incidence of Autism
  • Dales, L, et al JAMA 2001 2851183-1185
  • Compared the number of autism cases reported in
    CA between 1980-94 with rates
    of MMR vaccination during the same period.
  • The incidence of autism exploded by 373, but the
    of children who received MMR
    vaccination by age 2 increased only moderately,
    from 72 to 82 over the 14-year period.
  • "There is no correlation to show that MMR
    vaccination is a
    major factor, or even a factor at all, in
    autism."
  • Kaye J, et al Brit Med Jour 2001322
  • Although the incidence of autism rose between
    1988-99, the
    prevalence of MMR vaccination remained constant
    at 97 during
    that period
  • Exposure to MMR cannot explain rapid increase in
    autism
  • Other factors are responsible for increase
  • Recognition of lesser forms of disease
  • Environmental factors Other?

14
MMR Vaccination Not Associated With Autism Danish
Study2002
  • 537,303 children born in Denmark between 1/1/91
    and 12/31/98 were
    studied.
  • 440,655/537,303 (82) had received the MMR
    vaccine.
  • 316 children diagnosed with autism and
  • 422 diagnosed with other autistic-spectrum
    disorders.
  • The risk of autism remained similar in vaccinated
    and unvaccinated children after taking into
    account factors such as birth weight, gestational
    age, socioeconomic status, mother's education and
    gender
  • The results of the large population-based study
    provide "strong evidence" that the measles, mumps
    and rubella (MMR) vaccine
    is not a cause of autism.
  • There was a lack of association between MMR
    vaccination and autism no
    matter how how the data was analyzed.

Madsen et al. N Engl J Med 20023471477-1482.
15
VaccinesBioterrorist Agents
  • Anthrax
  • Cell-free culture of an avirulent,
    non-encapsulated,
    derivative of a bovine isolate-V770
  • 2-dose efficacy in monkeys
  • Estimated 90 effective against cutaneous
    anthrax
  • Botulism
  • Pentavalent toxoid (A-E)
  • 3 doses 100 effacicious in primates
  • Tulermia
  • Live attenuated vaccine
  • 80 protection
  • Plaque
  • Suspension of killed Y. pestis
  • Questionable immunity
  • Smallpox
  • Vaccinia vaccine Effective in one dose Side
    effects
  • VHF
  • No vaccine available

16
Emerging/Re-emerging Diseases
  • Newly recognized
  • Changes in known organisms

17
(No Transcript)
18
Emerging / Re-emerging
Diseases
  • HIV/AIDS/Opportunistic infections
  • Hepatitis A-G, Other ?
  • Herpes, Flu, Other viral diseases
  • Candiaiasis, Other fungal diseases
  • Bacterial/Drug resistant bacterial
  • E. coli 015.7H7
  • Other food/H2O-borne
  • S. Pneumonia, MRSA, VRSA
  • Vancomycin resistant Enterococcus
  • Multiple-drug resistant TB (MDRTB)
  • Bio-engineered agents

19
Emerging Viral Diseases
20
  • First reported 6/5/81 by CDC

June 5, 1981 / Vol. 30/ No. 21
Epidemiologic Notes and Reports Pneumocystis
Pneumonia --- Los Angeles In the period October
1980-May 1981, 5 young men,
all active homosexuals, were treated for
biopsy-confirmed Pneumocystis carinii pneumonia
at 3 different hospitals in Los Angeles,
California. Two of the patients died. All 5
patients had laboratory-confirmed previous or
current cytomegalovirus (CMV) infection and
candidal mucosal infection. Case reports of these
patients follow.

21
HIV
  • Very dynamic virus
  • 109 viral particles/day
  • Loss of 108-109 CD4 cells/day
  • Replicate every two days
  • 680,000 viral particles produced and cleared
    daily
  • 95 of virus produced from newly infected cells

22
HIV Twenty Years in Review
  • 1981 The first cases of AIDS reported
  • June 5, 1981 (MMWR 198130250)
  • 1982 Term AIDS replaces GRID
  • 1983 Universal precautions introduced
  • MMWR 198332101
  • The virus that causes AIDS identified
  • Gallo- HTLV III Montagnier-LAV
  • Name changed to human immunodeficiency virus
    (HIV)
  • 1985 First serologic test for HIV licensed by
    FDA
  • Rock Hudson died of AIDS on 10/2/85
  • 1986 AZT approved by FDA
  • Record approval time of 6 months

Bartlett JG Hopkins HIV Report, July 2001
23
HIV Twenty Years in Review
  • 1989 U.S. AIDS cases reported at 100,000
  • 1991 Estimated HIV infected in USA 1.5 million
  • Magic Johnson announces he is HIV positive
  • 1993 Multiple drugs fail in clinical trials
  • Period of extreme pessimism for HIV infected
  • 1995 First protease inhibitor approved
  • Inverase,saquinivir
  • HIV kinetics reported at 10 billion virions/day

Bartlett JG Hopkins HIV Report, July 2001
24
HIV Twenty Years in Review
  • 1996
  • HIV viral load testing
  • Becomes major method to assess ART
  • Mellors J Ann Intern Med 1997126946
  • ACTG 076 shows benefit of AZT in reducing
    perinatal transmission
  • NEJM 19963351621
  • Initial reports of benefit of HAART
  • Ritonavir and indinavir approved
  • Fisrt NNRTI, nevirapine approved
  • First triple combination HAART study
  • Eradication of HIV might be possible with HAART
  • Dr. David Ho Time Man of the Year

Bartlett JG Hopkins HIV Report, July 2001
25
HIV Twenty Years in Review
  • 1997 13 decrease in AIDS deaths
  • 60-80 reduction in new AIDS-defining conditions,
    hospitalizations and deaths
  • Palella et al, NEJM 1998338853,
  • Mocroft at al, Lancet 19983521725
  • 1999 HIV spread to humans from chimpanzees
  • Occurred in Africa decades before recognition
  • 2000 AIDS pandemic raging in Third World
  • 36.1 million people infected with HIV
  • 21.8 million deaths
  • 14,000-16,000 new infections/day
  • 2001 Two distinct epidemics

Bartlett JG Hopkins HIV Report, July 2001
26
HIV Natural History
  • Viral Transmision
  • Primary HIV INfection
  • Seroconversion syndrome
    Symptomatic Fever (96),
    Adenopathy (74),Pharyngitis (70), Rash (70),
    Other SymptomsOnset
    2-4 weeks,
    but 10 months documented
    Frequently diagnosis
    overlooked
  • Seroconversion

    3-12 weeks, median 63 days
    95
    seroconversion in 5.8 months

Bartlett J Medical Mgmt. of HIV Disease, 2001
27
Seroconversion Syndrome
  • Symptoms appear 2-4 weeks after transmission
  • Fever
  • Sore throat
  • Lymphadenopathy
  • Rash
  • Maculopapular
  • Resolves spontaneously

28
HIV Natural History
  • Clinical Latent Period
    Asymptomatic - May have PGL
    Viral set point at
    6 month Equilibrium between
    immune system and HIV Persists for years
    Gradual,
    relentless degradation of immune function
  • Early Symptomatic HIV Infection
    CD4 Opportunistic Infection(s)
  • AIDS CD4
  • Advanced HIV Infection
    CD4 Infection(s) Death

Bartlett J Medical Mgmt. of HIV Disease, 2001
29
How Is HIV Spread?
  • Routes of Transmission
  • Sexual
  • IDU
  • Inhalation drug abuse
  • Exposure to blood/blood products
  • Occupational exposure
  • Mother to child
  • Breast feeding

30
Cocaine Abuse
  • Cocaine abuse is a growing problem and
    interaction with drugs commonly use in dentistry
    can be lethal
  • Patients often do not report cocaine usage
  • Potential adverse interaction between cocaine and
    adrenergic vasoconstrictors and other drugs
  • Suspect cocaine use when
  • Confronted by patient showing agitation, tremor,
    sympathetic arousal and dysrhythmias
  • Damage to nasal septum or skin lesions
    on the forearms
  • Vasoconstrictors should not be used for
    24 hours after
    cocaine

Yagiela J. JAMA Vol. 130 May 1999, 701-709.
31
Mother-to-Child Transmission Global
Situation
  • Estimated 2.4 million HIV-positive women give

    birth annually to 600,000 HIV-positive babies
  • 1800 new infections each day
  • 90 in sub-Saharan Africa
  • Transmission rates
  • USA/Europe 1330 without ART,
    approaching 13 with ART
  • Developing countries 2043 without ART, lower
    rates with ART, even with short-course therapy
  • Breast feeding for 6 months
  • Additional 510 infections, with the highest
    rates of transmission occurring in the first and
    second months post-partum

Wiktor SZ, et al. XIIIth IAC, Durban, 2000.
Abstract 354
32
Mother-to-Child TransmissionPrevention
  • Regimen recommended for pregnant HIV women
  • Standard Reduces HIV transmission by two thirds
  • Zidoduvine (ZDV) 100mg 5 x daily beginning week
    14-34 of gestation and continued until delivery
  • During labor 2mg/kg infusion for 1 hr then a
    continuous infusion of 1mg/kg per hr until
    delivery
  • 8-12 hrs after birth, infants given oral ZDV
    syrup 2mg/kg q6h for the 1st 6 weeks of life
  • Short Course
  • Nevirapine (NVP) 200 mg tablet
  • Administered to mother once at the onset of labor
  • NVP 200 mg to infant within 72 hours of birth
  • 50 decrease in HIV transmission compared to ZDV

www.hivatis.org August 30, 2002
33
Adults and Children With HIV/AIDS, 12/31/02
Eastern Europe Central \Asia 1,200,000
North America 980,000
Western Europe 570,000
East Asia Pacific 1,200,000
North Africa Middle East 550,000
Caribbean 440,000
South South-East Asia 6,000,000
Latin America 1,500,000
Sub Saharan Africa 29,400,000
Australia New Zealand 15,000
People living with HIV/AIDS
.......................... 42 million New HIV
infections in 2002 ..........................
. 5 million Deaths due to HIV/AIDS in 2002
.................... 3.1 million
34
Treatment of HIV Disease
  • HAART
  • Management of opportunistic infection(s)

35
Current HAART Medications Abbreviations
  • NRTI
  • Abacavir ABC
  • Didanosine ddI
  • Lamivudine 3TC
  • Stavudine d4T
  • Zidovudine ZDV
  • Zalcitabine ddC
  • Trizivir TRZ
  • NNRTI
  • Delavirdine DLV
  • Efavirenz EFV
  • Nevirapine NVP
  • PI
  • Amprenavir AMP
  • Indinavir IND
  • Lopinavir LOP
  • Nelfinavir NLF
  • Ritonavir RIT
  • Saquinavir SAQ
  • soft gel SGC
  • hard gel HGC

36
Drugs Commonly Used in Dentistry That Should Not
Be Used With Protease Inhibitors or NNRTIs
Nevirapine No drugs contraindicated
Non-nucleoside reverse transcriptase
inhibitors Alternatives Analgesics-ASA,
oxycodone, acetaminophen Antihistamine-loratadin
e, fexofenadine, cetirizine Psycotrophic-temazep
am, forazepam  
Modified from Bartlett JG Gallant J Medical
Management of HIV Infection, 2001-2002 Edition
37
Adverse Effects
  • NRTIs
  • Zidovudine
  • HA, GI
  • Bone marrow suppression
  • Didanosine
  • GI intolerance
  • Pancreatitis
  • Stavudine
  • Peripheral neuropathy
  • Zalcitabine
  • Peripheral neuropathy
  • Abacavir
  • HA, GI
  • Hypersensitivity reaction
  • NNRTIs
  • Nevirapine
  • Rash, liver
  • Delavirdine
  • Rash
  • Efavirenz
  • Teratogenic in primates,
  • CNS, rash
  • PIs
  • Indinavir
  • Nephrolithiasis
  • Ritonavir
  • GI intolerance
  • Nelfinavir
  • Diarrhea
  • Amprenavir
  • GI intolerance
  • Lopinavir
  • diarrhea

38
Metabolic and Morphologic Abnormalities
  • Morphologic
  • Lipo-atrophy
  • Central fat accumulation
  • Fat deposition
  • Buffalo hump
  • Lipomas
  • Ectodermal
    dysplasia (?)
  • Metabolic
  • Elevated blood lipids
  • Cholesterol
  • Triglycerides
  • Elevated C-peptide
  • Insulin resistance,
  • Elevated blood glucose
  • Diabetes mellitus
  • Osteopenia (?)
  • Avascular necrosis (?)

Carr A. (State of the Art Lecture) 8th CROI,
Chicago, 2001. Issues in Metabolic Complications
39
Hepatitisand Liver Disease
40
Liver Disease
  • 500-1000 therapeutic agents implicated in
    hepatitis
  • 15-20 million Americans are alcoholics

41
Chronic Liver Disease
  • Tenth leading cause
    of death in
    USA
  • 25,000 deaths/year
  • 1 of all deaths
  • 40 of chronic liver
    disease HCV-related
  • 8-10,000 deaths/year.
  • HCV associated end stage liver disease is the
    most frequent
    indication for liver transplant
  • As HCV population ages incidence of chronic
    liver disease could
    increase substantially

MMWR 1998 Vol. 47/ No. RR-19
42
Hepatitis Inflammation of the Liver
  • Hepatitis
  • Asymptomatic - anicteric
  • Mild symptomatic - anicteric
  • Classic icteric infection
  • Fulminant hepatitis
  • Chronic hepatitis

43

Viral Hepatitis - Overview

Type of Hepatitis
A
B
C
D
E
Source of
feces
blood/ blood-derived/body fluids
feces
virus
Route of
Percutaneous/permucosal
fecal-oral
fecal-oral
transmission
Chronic
no
yes
yes
yes
no
infection
Prevention
pre/post-
pre/post-
blood donor
ensure safe
pre/post-
exposure
exposure
screening
exposure
drinking
immunization
immunization
risk behavior
immunization
water
modification
risk behavior
modification
44
Viral HepatitisSherker, AH Hepatitis, 1998
45
Hepatitis A
Family
Picornavirus
Incubation
15-40 days
Onset
Usually acute
Prodrome
None
Transmission
Oral/fecal
Carrier state
None
Mortality
0.1-0.2
46
Hepatitis B
Family Incubation Onset Prodrome Transmission

Carrier state
Mortality
Hepadnavirus 50-180 days Slow, insidious Sometimes
Blood, sex, perinatal Yes (5-10) 1-2
47
Serologic Tests for HBV Infection
CDC, MMWR April 27, 2001/ Vol. 50 /No. RR-5
48
Hepatitis C
Flavivirus 1-5 months Insidious Sometime

Parenteral, sex 85 70
Family Incubation Onset Prodrome Transmission
Carrier state Chronic disease
Mortality
1-2 Prevalence 1.8 USA
49
Hepatitis C Virus
  • Acute Infection
  • HCV-RNA detectable in 1-3 weeks post-exposure
  • All patients develop liver cell injury
  • Documented by increased ALT occurring within
    average of 50 days
    (range 15-150)
  • Majority are asymptomatic and anicteric
  • 25-35 develop malaise, anorexia, weakness
    some become
    icteric fulminent liver failure-rare
  • HCV-antibody almost always detectable
  • Only 15 of cases self-limiting
    disappearance of
    HCV-antibody
    Management of Hepatitis C NIH
    Consensus Statement 1997 15(3)1-41

50
Hepatitis C Virus
  • Chronic Infection
  • At least 85 of patients fail to clear the virus
    within 6 months
  • All have anti-HCVor HCV-RNA
  • One in three have normal ALT
  • Clinical course insidious usually w/o symptoms in
    the 1st two decades
  • Progression may lead to inflammation, liver cell
    death and fibrosis
  • Necroinflammatory changes severe fibrosis can
    progress to cirrhosis which develops in 20 of
    patients and marks transition to uncompensated
    liver disease
  • Management of Hepatitis C NIH Consensus
    Statement 1997 15(3)1-41

51
Hepatitis C Virus
  • Hepatitis C rate of
    chronic disease 80
  • 35,000 new infection/yr
  • HCV has high
    propensity to mutate
  • Escapes immune surveillance
  • Lack of vigorous
    T-cell response promotes
    chronicity

NIH Consensus Development Conference, 2002
52
Hepatitis C Virus
  • Infects 1.8 of general population
  • About 4 million Americans
  • Highest prevalence
  • Adults aged 40-59 yrs
  • 6.1 of African Americans
  • 8-10,000 deaths/yr from chronic infection
  • Latency period for up to 20 years
  • Occupational transmission documented
  • 2-5 risk
  • 70- 90 of IDUs chronically infected
  • Rapidly acquired in IDUs
  • 50-80 acquisition in 6-12 months
  • Homeless, inmates and hemophiliacs 15-50

NIH Consensus Development Conference, 2002
53
HCV Testing
  • Two primary tests available for
    detection of HCV antibodies
  • Anti-hepatitis C antibody
    (anti-HCV Ab)
  • EIA
  • Enzyme immunoassays
  • RIBA
  • Recombinant immunoblot assays

NIH Consensus Development Conference, 2002
54
HCV Testing- EIA
  • First HCV EIA developed in 1989
  • Three generations of EIA since
  • EIA is main screening test for HCV
  • Advantages
  • Assays are easy to perform
  • Inexpensive
  • Highly sensitive, specificity not established
  • Disadvantages
  • Require confirmatory assay for HCV diagnosis
  • False positives in low risk and in pts with
    autoimmune disease

Bernstein D, Medscape, Gastroenterology Clinical
Management Volume1 //I.d.medscape.com/Medscape/gas
tro/ClinicalMgmt NIH Consensus Development
Conference. 1997 March 24-26 15(3)1-41.
55
Hepatitis D
Satellite
Family
Incubation
21-90 days
Onset
Usually acute
Prodrome
Unknown
Transmission
Usually parenteral
Chronicity
Yes
Mortality
2-20
56
Hepatitis E
Family
Calcivirus
Incubation
2-9 weeks
Onset
Usually acute
Prodrome
Not present
Transmission
Oral/fecal,food/H2O
3rd World
Carrier state
None
Mortality
1-2 in gen. pop.
20 in pregnancy
57
Hepatitis G
Flavivirus Unknown Parenteral, sex? Probable Unkno
wn Unknown 1.7 blood donors
  • Family
  • Incubation
  • Transmission
  • Carrier state
  • Chronic disease
  • Mortality
  • Prevalence

58
Hepatitis
  • SIGNS AND SYMPTOMS
  • Fatigue, nausea, vomiting, diarrhea,
  • Joint and muscle pain,
  • Jaundice, hepatomegaly,
  • Abdominal and gastric distention,
  • Clay colored stools, dark urine,
  • Fever, bruising, rash, chills,
  • Anorexia ,distaste for cigarettes and food

59
Liver Dysfunction
  • Inflammation
  • Monitored by evaluating serum liver
    enzyme levels
  • AST - Aspartate aminotransferase
  • ALT - Alanine aminotransferase
  • Transaminase levels also useful in
    determining the course of the disease
  • As values decrease, the patient may be
    resolving the infection.

60
AST - SGOTALT - SGPT
  • Jaundice
  • 2.5 mg/100 ml Bilirubin

61
Medical Management
of Hepatitis
  • Non specific - palliative/bed rest
  • Nutrition and high caloric diet
  • Corticosteroids
  • Interferon therapy
  • Antiviral therapy
  • Combination therapy

62
Hepatitis Treatment
  • 1. Interferon Therapy
  • Regimen 3 MU 3X/Week X 12 Months
  • Infergen Interferon alfa-1
  • Intron A Interferon alfa-2a
  • Referon-A Interferon alfa-2a
  • Rebetron Rebetol (ribavirin)
    Interferon alfa
    2b
  • 2. Antivirals/antiretrovirals
  • 3TC (Epivir-HBV) FDA Approved
  • Adefovir other antiretroviral drugs
  • Famciclovir other antivirals

63
Dental Management of
the Hepatitis
Patient
64
Laboratory Tests
  • Latest CD4 count, viral load
  • CBC with differential
    WBC 1,000 CELLS/mm3
  • Platelet count

    100,000 CELLS/mm3
  • PT, PTT, INR, bleeding time
  • PPD
  • LFTS (ALT, AST)

65
Common Laboratory Tests In Liver
Disease
  • ALT - Alanine Aminotransferase
  • Enzyme produced in hepatocytes
  • Increases when hepatocytes damaged/killed
  • Level may correlate with degree of inflammation
  • Correlation variable Biopsy needed for accuracy
  • AST - Aspartate Aminotransferase
  • Similar to ALT but less specific for liver
  • Alakaline Phosphatase
  • Enzyme(s) produced in bile ducts
  • Also in intestine, kidney, placenta and bone

  • Elevation suggests disease of bile ducts

66
Coagulation Tests
  • Indicate patients clotting ability
  • Increase indicates abnormal clotting
    mechanism(s)
  • Coagulation tests
    - Prothrombin time (PT)
    -
    International normalized ratio (INR)

    - Partial thromboplastin time
    (PTT) - Bleeding
    time

67
PROTHROMBIN TIME (PT)
  • NORMAL VALUE
  • 11-16 SECONDS

Note prior to any surgical procedure
patient should be checked to ensure it
is less
than twice normal.
68
Management of the Medically Compromised Dental
Patient
  • Assess patient
    Pre-op, during
    post-op for
    susceptibility to
  • Bleeding/hemostasis
  • Infection
  • Drug interaction(s)/ contraindications
  • Ability to withstand dental treatment

69
International Normalized Ratio
(INR)
Evaluates level of anticoagulation
  • INR for patients not on anticoagulants
  • 0.9-1.1
  • INR for patients on anticoagulants (controlled)

  • 2.0-3.0
  • INR for patients with prosthetic
    valves or MI
  • 2.5-3.5

70
Treatment of the Hepatitis Patient
  • The major complication encountered with treatment
    of the hepatitis patient is hemorrhage.
  • Coagulation tests should include
  • Platelet Count,
  • Bleeding Time,
  • International Normalized Ratio (INR)
    or Prothrobin Time (PT)
  • Partial Thromboplastin Time (PTT)

71
Treatment of the Hepatitis Patient
  • If coagulation tests are not within
    normal limits, consider for
    all surgical procedures
  • Avoidance of
    aspirin containing products
  • A 10 mg dose of Vitamin K administered IM or IV
    prior to dental
    procedures.
  • Re-evaluation PRN

72
Treatment of the Hepatitis Patient
  • To avoid stress to the patients coagulation
    mechanisms all surgical dental procedures should
    be
  • Scheduled in small increments.
  • Gelfoam or topical thrombin
    should be used in
    extraction
    sites And
  • Suturing of all overlying
    tissues/gingiva should be

    considered to control

    hemorrhage after surgery

73
Treatment of the Hepatitis Patient
  • Pressure dressings on
    operative sites as
    necessary
  • Soft diet for 48 to 72 hours after surgical
    procedure
  • Avoid substances that may cause hepatic
    inflammation.

74
Use with Caution
DRUGS METABOLIZED BY THE LIVER
75
Drugs Metabolized By The
Liver
  • Local Anesthetics
  • Lidocaine (Xylocaine)
  • Mepivacine (Carbocaine)
  • Prilocaine (Citinest)
  • Bupivacaine (Marcaine)

76
Drugs Metabolized By The
Liver
  • Analgesics
  • Aspirin
  • Acetaminophen
  • NSAIDS
  • Codeine
  • Meperidine (Demerol)

77
Drugs Metabolized By The
Liver
  • Antibiotics
  • Amoxicillin
  • Ampicillin
  • Tetracycline
  • Erythromycin
  • Clindamycin

78
Drugs Metabolized By The
Liver
  • Sedatives
  • Diazepam (Valium)
  • Barbiturates
  • Chlordiazepoxide (Librium)

79
Human Herpes Viruses
80
Human Herpesviruses
  • Alpha Herpesviruses
  • Herpes Simplex Virus Type 1 (HSV-1)
  • Herpes Simplex Virus Type 2 (HSV-2)
  • Varicella Zoster Virus (HZV)
  • Beta Herpesviruses
  • Cytomegalovirus (CMV)
  • Human Herpesvirus Type 6 (HHV-6)
  • Human Herpesvirus Type 7 (HHV-7)
  • Gamma Herpesviruses
  • Epstein-barr Virus (EBV)
  • Human Herpesvirus Type 8 (HHV-8)

  • Kaposis Sarcoma Asso. Herpesvirus

Sandstrom and Whitley
International Herpes Management Forum Strategies
Workshop and 3rd Annual Mtg, 1999

81
Viruses Herpes HSV-1 2
  • HSV-1
  • Oral/genital/mucocutaneous lesions

  • Acute gingivostomatitis
  • Pharyngitis

  • Herpes labialis

  • Keratoconjunctivitis
  • Encephalitis
  • Herpetic Whitlow

  • HSV-2
  • Oral/genital/mucocutaneous lesions
  • At least 14 persons 12 y.o. infected

  • 70-90 asymptomatic shedding
  • Only about 20 of HSV-2 Ab know they are infected

82
Varicella-Zoster (VZV)
  • Chickenpox Ubiquitous infection of childhood
  • Primary infection results in the characteristic
    disseminated cutaneous lesions.
  • The virus then establishes lifelong latency in
    dorsal root ganglia from whence it may reactivate
    to cause localized cutaneous eruptions known as
    herpes zoster or shingles.
  • Herpes zoster usually occurs later in life as a
    consequence of immunosuppressive illness or
    immunosuppressive medical therapy.
  • Declining VZV-specific immunity later in life is
    associated with an increased risk of herpes
    zoster.

83
Herpes Viruses
  • EBV

  • Infects 85 of population

  • Agent of infectious mononucleosis
  • Cause of oral hairy leukoplakia


  • Oncogenic Burkitts Lymphoma
  • Linked to Hodgkins Disease/ other malignancies
  • CMV

  • Problematic in immumocomp. pts Retinitis,
    enteritis
  • Linked to vasculopathies, CAD?

  • Role in organ transplant rejection

  • Other graft/host involvement

84
Herpes Simplex VirusInitial Treatment
  • Mild HSV
  • acyclovir, (Zovirex) 400 mg, po, tid or
  • famciclovir, (Famvir) 250 mg, po, tid or
  • valacyclovir, (Valtrex) 1.0 gm bid
  • All given 7-10 days
  • Severe or refractory HSV
  • acyclovir up to 800 mg, po, X 5 days or
  • acyclovir 15-30 mg/kg IV/day X at least 7 days
  • valacyclovir 1 gm, po, bid-tid X 7-10 days

Barlett J, Medical Management of HIV Infection
2000-2001
85
Herpes Simplex VirusTopical Treatment
  • Recurrent Herpes Labialis
  • Penciclovir 1 cream Rx
  • Denavir 1.5 gram tube 10mg penciclovir/gram
  • Apply every 2 hrs when awake X 4 Days
  • As soon as prodromal symptoms appear
  • Docosanol 10 cream OTC
  • Apply 5x daily when awake X 4 days
  • As soon as prodromal symptoms appear

Siegle M, J Amer Dent Asso. 2002 1331245-49.
86
Human PapillomavirusHPV
87
Human Papillomavirus
  • Most common viral STD
  • Infects about 1/3 of sexually active
    population in USA
  • 60 strains have been identified
  • 25 strains associated with genital
    tract
    infections/cancer
  • Strongly associated with
  • Cervical cancer
  • Causative agent
  • Oral cancer
  • Peri-anal/testicular cancer
  • Especially severe in HIV infected

88
Papilloma
Focal Epithelial Hyperplasia (FEH)
  • Etiological agent
  • Human papilloma virus (HPV)
  • Wart
  • Clinical
    appearance
  • Flat (FEH)
  • Siky
  • Cauliflower-like

89
WNV In USA
WNV is spreading rapidly throughout the
country
12/11/02
90
WNV in USA 12/31/2002
  • In 2002, 5 States Il, MI, OH, LA and IN accounted
    for
  • 62.2 of WNV cases
  • 70.5 of deaths

www.cdc.gov/od/oc/media/wncount.htm
91
West Nile Virus
Clinical Presentation
  • Incubation period 3 - 14 days
  • 20 develop West Nile fever
  • 1 in 150 develop meningoencephalitis
  • Advanced age primary risk factor for
    severe neurological disease
    and death
  • Mild dengue-like illness of sudden onset
  • Duration 3 - 6 days
  • Fever, lymphadenopathy, headache,
    abdominal pain, vomiting, rash,
    conjunctivitis, eye pain,
    anorexia
  • Symptoms of West Nile fever in contemporary
    outbreaks not fully studied

92
West Nile Virus
Clues and Clinical
Presentation
  • Suspect WNV when
  • Symptoms consistent with WNV
  • Unexplained bird or horse deaths
  • Mosquito season
  • Age 50 years
  • Symptoms
  • Most cases asymptomatic or mild dengue-like
    illness
  • Incubation period usually 5 (3) to 15 days
  • Fever, lymphadenopathy, headache
  • Abdominal pain, vomiting, rash, conjunctivitis
  • Muscle weakness and /or flaccid paralysis,
    hyporeflexia
  • EMG/NCV showing axonal neuropathy
  • Lymphocytopenia
  • MRI
  • Shows enhancement of leptomeninges and/or
    periventricular area
  • CNS involvement and death in minority of cases

93
Severe Acute Respiratory Syndrome (SARS)
94
Severe Acute Respiratory Syndrome (SARS)
  • The Initial Epidemic
  • Outbreak of atypical pneumonia in Hong Kong in
    March 2003
  • Between 03/11/03 and 03/25/03 156 patients
    were
    hospitalized with SARS
  • 138 were identified as secondary or tertiary
    cases as a
    result of exposure to index case(s)
  • 112 secondary cases
  • 26 tertiary cases
  • Includes 69 HCWs
  • 20 MDs
  • 34 Nurses
  • 15 Allied HCWs
  • 54 patients on ward or visitors
  • 16 medical students
  • 32 of the 138 patients (23.2) had severe
    respiratory failure
  • 5 patients died (3.6)
  • All had been hospitalized with a major medical
    condition

Lee N et al. NEJM April 7, 2003. www.nejm.org
95
Severe Acute Respiratory Syndrome (SARS)
  • The Clinical Presentation- Initial 138 Cases
  • Incubation period was 2-10 days from initial
    exposure to onset of
    fever
  • Median incubation period was 6 days
  • The most common clinical symptoms were
  • Fever (100) 100.50
  • Chills, rigors or both (73.2)
  • Myalgia (60.9)
  • Cough (57.3)
  • Headache (55.8)
  • Dizziness (42.8)
  • Less common symptoms included
  • Sore throat, sputum production, coryza,

    nausea, vomiting, and diarrhea

Lee N et al. NEJM April 7, 2003. www.nejm.org
96
Severe Acute Respiratory Syndrome (SARS)
  • Routes of Transmission
  • The principal way SARS appears to be spread is
    through droplet transmission1,2
  • Namely, when a SARS patient coughs or sneezes
    droplets into the air and
    someone else breathes them in.
  • It is possible that SARS can be transmitted
    through the air or from objects that have become
    contaminated.1,2
  • People at risk 1,2
  • Direct close contact with an infected person
  • Sharing a household with a SARS patient
  • HCWs who did not use infection control
    procedures while caring
    for a SARS patient.
  • In the United States, there is no indication
    of
    community transmission at this time.1,2
  • CDC. April 4, 2003. http//www.cdc.gov/ncidod/sars
    /faq.htm.
  • http//www.ada.org/prof/prac/issues/topics/sars.ht
    ml

97
Severe Acute Respiratory Syndrome (SARS)
  • Respiratory illness of viral etiology with onset
    since February 1, 2003, and
    the following criteria
  • Measured temperature 100.5F (38 C)

    AND
  • One or more clinical findings of respiratory
    illness
  • Cough
  • Shortness of breath
  • Difficulty breathing
  • Hypoxia
  • Radiographic findings of either pneumonia
    or acute
    respiratory distress syndrome
  • AND

http//www.cdc.gov/ncidod/sars/casedefinition.htm
98
Severe Acute Respiratory Syndrome (SARS)
  • Travel within 10 days of onset of symptoms
    to an area with documented or
    suspected community transmission of SARS
  • Peoples' Republic of China
  • Mainland China
  • Hong Kong Special Administrative Region
  • Hanoi, Vietnam
  • Singapore
  • Toronto, Canada (04/21/03)
  • OR

http//www.cdc.gov/ncidod/sars/casedefinition.htm
99
Severe Acute Respiratory Syndrome (SARS)
  • Close contact within 10 days of onset of symptoms
    with either a person with a respiratory illness
    who traveled to a SARS area or a person known to
    be a suspect SARS case.
  • Close contact is defined as having
  • Cared for
  • Lived with
  • Direct contact with respiratory secretions and/or
    body fluids of a patient known to be suspect SARS
    case.

http//www.cdc.gov/ncidod/sars/casedefinition.htm
100
Severe Acute Respiratory Syndrome (SARS)Case
Definition 04/20/03
  • Suspected Case
  • Travel within 10 days of onset of symptoms to an
    area with documented or suspected community
    transmission of SARS
  • Excludes areas with secondary cases limited to
    healthcare workers or direct household contacts)
  • Travel includes transit in an airport in an area
    with documented or suspected community
    transmission of SARS. Areas with documented or
    suspected community transmission of SARS
  • People's Republic of China
  • Mainland China
  • Hong Kong Special Administrative Region
  • Hanoi, Vietnam
  • Singapore
  • Toronto, Canada.

http//www.cdc.gov/ncidod/sars/casedefinition.htm
101
Severe Acute Respiratory Syndrome (SARS)Case
Definition 04/20/03
  • Suspected Case
  • Close contact within 10 days of onset of symptoms
    with a person
    known to be a suspect SARS case.
  • Close contact is defined as having cared for,
    having lived with, or having direct contact with
    respiratory secretions and/or body fluids of a
    patient known to be suspect SARS case.
  • Probable Case
  • A suspected case with one of the following
  • Radiographic evidence of pneumonia or
    respiratory
    distress syndrome
  • Autopsy findings consistent with respiratory
    distress
    syndrome without an identifiable cause

http//www.cdc.gov/ncidod/sars/casedefinition.htm
102
Severe Acute Respiratory Syndrome (SARS)
  • Cause of SARS
  • Scientists at CDC and other
    laboratories have detected
    a
    previously unrecognized
    coronavirus in patients with SARS.1-4
  • Confirmed as causative agent by
    WHO on 04/16/03
  • Virus a member of the coronavirus family,
    never before seen in humans

1. http//www.cdc.gov/ncidod/sars/casedefinition.h
tm 2. Peiris J et al, Lancet 2003
http//image.thelancet.com/extras/03art3477web.pdf
3. Drosten C et al. NEJM 2003 www.nejm.org 4.
Ksiazek T et al. NEJM 2003 www.nejm.org
103
Severe Acute Respiratory Syndrome (SARS)
  • Cause of SARS
  • Coronaviruses are a group of viruses

    that have a halo or crown-like (corona)
    appearance when
    viewed under a
    microscope.
  • These viruses are a common cause of mild to
    moderate upper-respiratory illness in humans
    and are associated with
    respiratory, gastrointestinal, liver and
    neurologic disease in animals.
  • Coronaviruses can survive in the environment for
    as long as three to four hours.

1. http//www.cdc.gov/ncidod/sars/casedefinition.h
tm 2. Peiris J et al, Lancet 2003
http//image.thelancet.com/extras/03art3477web.pdf
3. Drosten C et al. NEJM 2003 www.nejm.org 4.
Ksiazek T et al. NEJM 2003 www.nejm.org
104
Severe Acute Respiratory Syndrome (SARS)Dental
School, University of Maryland
  • Precautions for Dental Patients Who
    May Have
    Been Exposed to SARS
  • While taking initial medical histories and at
    periodic updates, all dental patients at the
    Dental School will routinely be asked about
  • Recent travel of patient or immediate family
    members to areas where SARS is
    endemic
  • Peoples' Republic of China
  • Mainland China
  • Hong Kong Special Administrative Region
  • Hanoi, Vietnam
  • Singapore
  • Toronto, Canada

DePaola L, 2003, University of Maryland Baltimore
105
Severe Acute Respiratory Syndrome (SARS)Dental
School, University of Maryland
  • Precautions for Dental Patients Who
    May Have
    Been Exposed to SARS
  • Recent respiratory illness
  • Cough
  • Shortness of breath
  • Difficulty breathing
  • Hypoxia
  • Radiographic findings of either pneumonia or

    acute respiratory distress syndrome
  • Close contact with anyone suspected of being
    infected with SARS
  • While taking initial medical histories and at
    periodic updates,
    all dental patients at the Dental School will
    routinely be
    asked whether they have a history of and/or
    S S suggestive
    of SARS

DePaola L, 2003, University of Maryland Baltimore
106
Severe Acute Respiratory Syndrome (SARS)Dental
School, University of Maryland
  • Precautions for Dental Patients Who
    May Have
    Been Exposed to SARS
  • Patients with a medical history or signs and
    symptoms of SARS will be immediately referred

    to the University of
    Maryland Medical System, or their private
    physician for medical evaluation for possible
    infectiousness.
  • Such patients should not remain in the Dental
    School any longer than required to arrange the
    referral.
  • Elective dental treatment will be deferred
    until a physician
    confirms that the patient
    does not have SARS.

DePaola L, 2003, University of Maryland Baltimore
107
Severe Acute Respiratory Syndrome (SARS)
  • Infection Control Procedures Suspected Cases1-3
  • Isolate patients in a separate waiting area
  • Give patients a surgical mask to wear
  • Instruct patients to cover mouth when coughing or
    sneezing
  • HCWS utilize surgical mask
  • Healthcare personnel should apply
  • Standard precautions
  • Hand hygiene
  • Soap and water or alcohol-based hand rub
  • Contact precautions when aerosol-generating
    procedures
    are being performed on patients who may have
    SARS.
  • Gloves, gown, and eyewear
  • Airborne precautions
  • Respiratory protective devices with a filter

    efficiency of greater than or equal to 95
  • Recommended with confirmed SARS patients
  • http//www.cdc.gov/ncidod/sars/infectioncontrol.ht
    m.
  • http//www.ada.org/prof/prac/issues/topics/sars.ht
    ml
  • DePaola L, 2003, University of Maryland Baltimore

108
Severe Acute Respiratory Syndrome (SARS)
  • Infection Control
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