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
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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
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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