Published on March 10, 2008
Emerging/Reemerging Diseases:Update 2003: Emerging/Reemerging Diseases: Update 2003 Louis G. DePaola, DDS, MS Professor Department of Diagnostic Sciences and Pathology Dental School University of Maryland Baltimore Emerging Infectious Diseases/Agents in the USA, 2003: 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 Emerging Infectious Diseases/Agents in the USA, 2003: 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 VaccinationsPrevent Disease: Vaccinations Prevent Disease Immunization Programs: Immunization Programs National guidelines for immunization of, and PEP for, HCP, which includes DHCP, are provided by the US Public Health Service’s 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 Immunization Programs: 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: Immunization Programs: 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 Vaccine Preventable Diseases Adults: 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 Vaccination of Pregnant Women: 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 Vaccine Preventable DiseasesChildren: Vaccine Preventable Diseases Children 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 Rubella: 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 < 12 weeks - Most dangerous Causes: Congenital Rubella Syndrome Multiple organ damage; death Prevention paramount!!! Vaccination: MMR National Immunization Program www.cdc.gov/nip MMR Vaccine Not Associated With Increased Incidence of Autism: MMR Vaccine Not Associated With Increased Incidence of Autism Dales, L, et al: JAMA; 2001; 285:1183-1185 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; 2001;322 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? MMR Vaccination Not Associated With Autism Danish Study:2002 : MMR Vaccination Not Associated With Autism Danish Study:2002 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 2002;347:1477-1482. VaccinesBioterrorist Agents: Vaccines Bioterrorist 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 Emerging/Re-emerging Diseases: Emerging/Re-emerging Diseases Newly recognized Changes in known organisms 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 015.7:H7 Other food/H2O-borne S. Pneumonia, MRSA, VRSA Vancomycin resistant Enterococcus Multiple-drug resistant TB (MDRTB) Bio-engineered agents Emerging / Re-emerging Diseases Emerging Viral Diseases: Emerging Viral Diseases Slide20: First reported 6/5/81 by CDC 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. June 5, 1981 / Vol. 30/ No. 21 HIV: 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 HIV: Twenty Years in Review: HIV: Twenty Years in Review 1981: The first cases of AIDS reported June 5, 1981 (MMWR 1981;30:250) 1982: Term AIDS replaces GRID 1983: Universal precautions introduced MMWR 1983;32:101 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 HIV: Twenty Years in Review: 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 HIV: Twenty Years in Review: HIV: Twenty Years in Review 1996: HIV viral load testing Becomes major method to assess ART Mellors J; Ann Intern Med 1997;126:946 ACTG 076 shows benefit of AZT in reducing perinatal transmission NEJM 1996;335:1621 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 HIV: Twenty Years in Review: 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 1998;338:853, Mocroft at al, Lancet 1998;352:1725 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 HIV Natural History: HIV Natural History Viral Transmision: Primary HIV INfection: Seroconversion syndrome: Symptomatic: Fever (96%), Adenopathy (74%),Pharyngitis (70%), Rash (70%), Other Symptoms;Onset 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 Slide27: Symptoms appear 2-4 weeks after transmission Fever Sore throat Lymphadenopathy Rash Maculopapular Resolves spontaneously Seroconversion Syndrome 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 < 500; Opportunistic Infection(s) AIDS: CD4 < 200; AIDS Defining Illness(s) Advanced HIV Infection: CD4 < 50; Serious Opportunistic Infection(s); Death HIV Natural History Bartlett J: Medical Mgmt. of HIV Disease, 2001 How Is HIV Spread?: How Is HIV Spread? Routes of Transmission: Sexual IDU Inhalation drug abuse Exposure to blood/blood products Occupational exposure Mother to child Breast feeding Cocaine Abuse: Cocaine Abuse Yagiela J. JAMA Vol. 130 May 1999, 701-709. Cocaine abuse is a growing problem and interaction with drugs commonly use in dentistry can be lethal Patient’s 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 Mother-to-Child Transmission Global Situation: Mother-to-Child Transmission Global Situation Wiktor SZ, et al. XIIIth IAC, Durban, 2000. Abstract 354 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 <1% (1000) in USA and Europe Transmission rates USA/Europe: 13–30% without ART, approaching 1–3% with ART Developing countries: 20–43% without ART, lower rates with ART, even with short-course therapy Breast feeding for 6 months Additional 5–10% infections, with the highest rates of transmission occurring in the first and second months post-partum Mother-to-Child TransmissionPrevention: Mother-to-Child Transmission Prevention 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 Adults and Children With HIV/AIDS, 12/31/02 : Adults and Children With HIV/AIDS, 12/31/02 North America 980,000 Western Europe 570,000 Eastern Europe & Central \Asia 1,200,000 Caribbean 440,000 Latin America 1,500,000 Sub Saharan Africa 29,400,000 North Africa & Middle East 550,000 East Asia & Pacific 1,200,000 South & South-East Asia 6,000,000 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 Treatment of HIV Disease: Treatment of HIV Disease HAART Management of opportunistic infection(s) Current HAART Medications & Abbreviations: 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 Drugs Commonly Used in Dentistry That Should Not Be Used With Protease Inhibitors or NNRTIs* : 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-loratadine, fexofenadine, cetirizine; Psycotrophic-temazepam, forazepam Modified from Bartlett JG & Gallant J: Medical Management of HIV Infection, 2001-2002 Edition Adverse Effects: 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 Metabolic and Morphologic Abnormalities: 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 Hepatitisand Liver Disease: Hepatitis and Liver Disease Liver Disease: Liver Disease 500-1000 therapeutic agents implicated in hepatitis 15-20 million Americans are alcoholics 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 Chronic Liver Disease MMWR 1998 Vol. 47/ No. RR-19 Hepatitis: Inflammation of the Liver: Hepatitis: Inflammation of the Liver Hepatitis Asymptomatic - anicteric Mild symptomatic - anicteric Classic icteric infection Fulminant hepatitis Chronic hepatitis Slide43: Viral Hepatitis - Overview A B C D E Source of virus feces blood/ blood-derived/body fluids feces Route of transmission fecal-oral Percutaneous/permucosal fecal-oral Chronic infection no yes yes yes no Prevention pre/post- exposure immunization pre/post- exposure immunization blood donor screening; risk behavior modification pre/post- exposure immunization; risk behavior modification ensure safe drinking water Type of Hepatitis Viral HepatitisSherker, AH: Hepatitis, 1998: Viral Hepatitis Sherker, AH: Hepatitis, 1998 Hepatitis A: Hepatitis A Family: Picornavirus Incubation: 15-40 days Onset: Usually acute Prodrome: None Transmission: Oral/fecal Carrier state: None Mortality: 0.1-0.2% Hepatitis B: 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% Serologic Tests for HBV Infection : Serologic Tests for HBV Infection CDC, MMWR April 27, 2001/ Vol. 50 /No. RR-5 Hepatitis C: Hepatitis C Family: Incubation: Onset: Prodrome: Transmission: Carrier state: Chronic disease: Mortality: 1-2% Prevalence: 1.8% USA Flavivirus 1-5 months Insidious Sometime Parenteral, sex > 85 % 70%; Hepatitis C Virus: 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 Hepatitis C Virus: 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 Slide51: 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 Hepatitis C Virus: 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 IDU’s chronically infected Rapidly acquired in IDU’s: 50-80 % acquisition in 6-12 months Homeless, inmates and hemophiliacs 15-50% NIH Consensus Development Conference, 2002 HCV Testing: 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 HCV Testing- EIA: 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/gastro/ClinicalMgmt NIH Consensus Development Conference. 1997 March 24-26; 15(3):1-41. Hepatitis D: Hepatitis D Family: Incubation: 21-90 days Onset: Usually acute Prodrome: Unknown Transmission: Usually parenteral Chronicity: Yes Mortality: 2-20% Satellite Hepatitis E: 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 Hepatitis G: Hepatitis G Family: Incubation: Transmission: Carrier state: Chronic disease: Mortality: Prevalence: Flavivirus Unknown Parenteral, sex? Probable Unknown Unknown 1.7% blood donors 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 Hepatitis Liver Dysfunction: 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. AST - SGOTALT - SGPT: AST - SGOT ALT - SGPT Jaundice: 2.5 mg/100 ml Bilirubin Medical Management of Hepatitis: Non specific - palliative/bed rest Nutrition and high caloric diet Corticosteroids Interferon therapy Antiviral therapy Combination therapy Medical Management of Hepatitis Hepatitis Treatment: 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 Dental Management of the Hepatitis Patient: Dental Management of the Hepatitis Patient Laboratory Tests: 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 LFT’S (ALT, AST) Common Laboratory Tests In Liver Disease: 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 Coagulation Tests: Coagulation Tests Indicate patient’s clotting ability Increase indicates abnormal clotting mechanism(s) Coagulation tests: - Prothrombin time (PT) - International normalized ratio (INR) - Partial thromboplastin time (PTT) - Bleeding time PROTHROMBIN TIME (PT): 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. Management of the Medically Compromised Dental Patient: 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 International Normalized Ratio (INR): International Normalized Ratio (INR) 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 Evaluates level of anticoagulation Slide70: 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) Slide71: 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 Treatment of the Hepatitis Patient Treatment of the Hepatitis Patient: Treatment of the Hepatitis Patient To avoid stress to the patient’s 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 Slide73: Pressure dressings on operative sites as necessary Soft diet for 48 to 72 hours after surgical procedure Avoid substances that may cause hepatic inflammation. Treatment of the Hepatitis Patient Use with Caution: Use with Caution DRUGS METABOLIZED BY THE LIVER Slide75: Drugs Metabolized By The Liver Local Anesthetics Lidocaine (Xylocaine) Mepivacine (Carbocaine) Prilocaine (Citinest) Bupivacaine (Marcaine) Slide76: Analgesics Aspirin Acetaminophen NSAIDS Codeine Meperidine (Demerol) Drugs Metabolized By The Liver Slide77: Antibiotics Amoxicillin Ampicillin Tetracycline Erythromycin Clindamycin Drugs Metabolized By The Liver Slide78: Drugs Metabolized By The Liver Sedatives Diazepam (Valium) Barbiturates Chlordiazepoxide (Librium) Human Herpes Viruses: Human Herpes Viruses Human Herpesviruses: 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) Kaposi’s Sarcoma Asso. Herpesvirus Sandstrom and Whitley: International Herpes Management Forum Strategies Workshop and 3rd Annual Mtg, 1999 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 1:4 persons > 12 y.o. infected; 70-90% asymptomatic shedding; Only about 20% of HSV-2 Ab+ know they are infected Viruses Herpes; HSV-1 & 2 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. Varicella-Zoster (VZV) Herpes Viruses : EBV: Infects > 85% of population; Agent of infectious mononucleosis Cause of oral hairy leukoplakia; Oncogenic: Burkitt’s Lymphoma; Linked to Hodgkin’s Disease/ other malignancies CMV: Problematic in immumocomp. pts; Retinitis, enteritis; Linked to vasculopathies, CAD? Role in organ transplant rejection; Other graft/host involvement Herpes Viruses 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 Herpes Simplex Virus Initial Treatment Barlett J, Medical Management of HIV Infection: 2000-2001 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 Herpes Simplex Virus Topical Treatment Siegle M, J Amer Dent Asso. 2002; 133:1245-49. Human PapillomavirusHPV: Human Papillomavirus HPV 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 Human Papillomavirus Papilloma; Focal Epithelial Hyperplasia (FEH): Papilloma; Focal Epithelial Hyperplasia (FEH) Etiological agent: Human papilloma virus (HPV) “Wart” Clinical appearance: Flat (FEH) Siky Cauliflower-like Slide89: WNV In USA WNV is spreading rapidly throughout the country 12/11/02 WNV in USA: 12/31/2002: WNV in USA: 12/31/2002 www.cdc.gov/od/oc/media/wncount.htm In 2002, 5 States Il, MI, OH, LA and IN accounted for 62.2 % of WNV cases 70.5% of deaths 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 West Nile Virus Clinical Presentation West Nile Virus Clues and Clinical Presentation: 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 Severe Acute Respiratory Syndrome (SARS): Severe Acute Respiratory Syndrome (SARS) Severe Acute Respiratory Syndrome (SARS) : 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 Severe Acute Respiratory Syndrome (SARS) : 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 Severe Acute Respiratory Syndrome (SARS) : 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.html Severe Acute Respiratory Syndrome (SARS) : Severe Acute Respiratory Syndrome (SARS) Respiratory illness of viral etiology with onset since February 1, 2003, and the following criteria: Measured temperature > 100.5°F (>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 Severe Acute Respiratory Syndrome (SARS) : 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 Severe Acute Respiratory Syndrome (SARS) : 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 Severe Acute Respiratory Syndrome (SARS)Case Definition 04/20/03 : 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 Severe Acute Respiratory Syndrome (SARS)Case Definition 04/20/03 : 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 Severe Acute Respiratory Syndrome (SARS) : 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.htm 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 Severe Acute Respiratory Syndrome (SARS) : 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.htm 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 Severe Acute Respiratory Syndrome (SARS)Dental School, University of Maryland : 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 Severe Acute Respiratory Syndrome (SARS)Dental School, University of Maryland : 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 Severe Acute Respiratory Syndrome (SARS)Dental School, University of Maryland : 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 Severe Acute Respiratory Syndrome (SARS) : Severe Acute Respiratory Syndrome (SARS) Infection Control Procedures Suspected Cases:1-3 Isolate patients in a separate waiting area Give patients a surgical mask to wear Instruct patients to cover mouth when coughing or sneezing HCW’S 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.htm. http://www.ada.org/prof/prac/issues/topics/sars.html DePaola L, 2003, University of Maryland Baltimore Severe Acute Respiratory Syndrome (SARS) : Severe Acute Respiratory Syndrome (SARS) Infection Control Procedures: For known SARS patients Due to rapid development of symptoms it is unlikely that SARS will be seen in the dental office HCW’S utilize NIOSH respirators appropriate for TB Defer all elective treatment until patient has been evaluated Refer patients for urgent/emergency care to locations equipped with TB Isolation Areas, i.e. local hospitals Follow the Guidelines for Preventing the Transmission of Mycobacterium tuberculosis in Health-Care Facilities http://www.cdc.gov/mmwr/preview/mmwrhtml/00035909.htm In summary, healthcare personnel should apply: Standard precautions Contact precautions Airborne precautions http://www.cdc.gov/ncidod/sars/infectioncontrol.htm. http://www.ada.org/prof/prac/issues/topics/sars.html DePaola L, 2003, University of Maryland Baltimore Slide109: An outbreak of unexplained illness occurred in May 1993 an area of the Southwest shared by NM, AZ, CO, and UT (Four Corners). A number of previously healthy young adults suddenly developed acute respiratory symptoms; about half soon died. A hantavirus, which is transmitted by rodents, was suspected. The virus named Sin Nombre virus (SNV) and its principal carrier, the deer mouse were positively identified. A "bumper crop" of rodents there, due to heavy rains during the spring of 1993. Determined that person to person transmission of SNV was unlikely. SNV had actually been present, but unrecognized, at least as early as 1959. Since the discovery in 1993, hantavirus pulmonary syndrome (HPS) has been identified in over half of the states of the U.S. Hantavirus Pulmonary Syndrome (HPS) Slide110: Influenza Influenza: Acute, febrile illness, usually self limited Headache, malaise, myalgias Fever - 104oF-106oF (days 1-3) URI symptoms Nasal discharge, sore throat, cough (days 2-7) Cervical adenopathy (children > adults) and rhonchi Attack rate: 10 - 40% Viral shedding: One day before - until 10 days after symptom onset Peak day 3-4 Shedding is prolonged in young children Transmission: Person to person via small particle aerosols Virus is relatively stable and favors low humidity and cool temperatures Influenza www.cdc.gov/ncidod/diseases/flu/fluvirus.htm Slide112: http://www.cdc.gov/nip/Flu/Public.htm#Facts Flu Facts: Flu Facts Influenza (flu) is a serious disease Flu is not a cold! It is far more dangerous than a bad cold The virus infects the lungs. It can lead to pneumonia/other sequellae. Every year in the USA approximately: 114,000 people are hospitalized 20,000 people die because of the flu. Most who die are over 65 years old. But small children less than 2 years old are as likely as those over 65 to have to go to the hospital because of the flu. http://www.cdc.gov/nip/Flu/Public.htm#Facts Influenza Vaccine: Influenza Vaccine www.cdc.gov/ncidod/diseases/flu/fluvirus.htm Type: Inactivated split or whole virus Route/schedule: 0.5 IM annually Efficacy: 70-90% Indications: Age > 65 Health care or day care workers Nursing home/chronic care residents Adults and children with pulmonary and cardiovascular disorders, chronic metabolic disease (diabetes mellitus), renal dysfunction, immunosuppression Teenagers and children on ASA Women in the 2nd and 3rd trimester of pregnancy Contraindications: Anaphylaxis to eggs Side effects: Local pain, occasional myalgias and rare allergic reactions Prevention and Control of InfluenzaRecommendations of the Advisory Committee on Immunization Practices (ACIP): Prevention and Control of Influenza Recommendations of the Advisory Committee on Immunization Practices (ACIP) The 2002 recommendations include five principal changes or updates: The optimal time to receive influenza vaccine is during Oct. and Nov. However, because of vaccine distribution delays during the past 2 years, ACIP recommends that vaccination efforts in Oct. focus on persons at greatest risk for influenza-related complications and health-care workers and that vaccination of other groups begin in November. Vaccination efforts for all groups should continue into Dec. and later, for as long as vaccine is available. Because young, otherwise healthy children are at increased risk for flu-related hospitalization, influenza vaccination of healthy children aged 6--23 months is encouraged when feasible. Vaccination of children aged >6 months who have certain medical conditions continues to be strongly recommended. The 2002--2003 trivalent vaccine virus strains are A/Moscow/10/99 (H3N2)-like, A/New Caledonia/20/99 (H1N1)-like, and B/Hong Kong/330/2001-like strains. A limited amount of influenza vaccine with reduced thimerosal content will be available for the 2002--2003 influenza season. MMWR. April 12, 2002 / 51(RR03);1-31 Slide116: http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5103a1.htm The 2002--2003 trivalent vaccine virus strains are: A/Moscow/10/99 (H3N2)-like A/New Caledonia/20/99 (H1N1)-like B/Hong Kong/330/2001-like strains Tuberculosis: Tuberculosis Tuberculosis (TB): Tuberculosis (TB) TB is not on the decline. One third of the world's population is infected with TB In 1999 TB caused 8,000 deaths/day The most deaths from TB in history 7- 8 million people become infected with TB/year 5-10 % of these people will develop active TB Between 1993 and 1996, TB increased 13 % TB accounts for more than 1/4 of all preventable adult deaths the developing world. nfid.org/factsheets The number one single infectious disease killer Tuberculosis (TB): Tuberculosis (TB) Someone is newly infected with TB every second ! TB is the leading killer of women TB outranks all causes of maternal mortality TB creates more orphans than any other infectious disease TB is the leading cause of death among HIV-positive individuals nfid.org/factsheets The number one single infectious disease killer Tuberculosis Transmission: Tuberculosis Transmission Caused by Mycobacterium tuberculosis Spread by: - Airborne route - Droplet nuclei Affected by: - Infectiousness of patient - Environmental conditions - Duration of exposure Most persons exposed do not become infected PathogenesisLatent M.tuberculosis Infection: Pathogenesis Latent M.tuberculosis Infection Inhaled droplet nuclei with M. tuberculosis : - Reach alveoli - Are taken up by alveolar macrophages - Reach regional lymph nodes - Enter bloodstream and disseminate Chest radiograph may have transient abnormalities Specific cell-mediated immune response controls further spread PathogenesisActive M. tuberculosis Infection: Pathogenesis Active M. tuberculosis Infection Active disease state Symptoms present: Cough Fever Chills Night sweats May be infectious Disease both treatable & preventable Diagnosis of Active TB: Diagnosis of Active TB History and epidemiologic clues Think TB!!! Chest X-ray Tuberculin skin test AFB smear AFB culture Nucleic acid amplification Fast but sensitivity poor in smear neg. Empiric treatment trial Slide124: Administering the Tuberculin Skin Test Inject intra-dermally: 0.1 ml of 5 TU PPD tuberculin Produce wheal: 6 mm to 10 mm in diameter Do not recap, bend, or break needles, or remove needles from syringes Follow universal precautions for infection control Slide125: Reading the Tuberculin Skin Test Read reaction: 48-72 hours after injection Measure only induration! Record reaction in millimeters Dental Offices: Dental Offices “….No specific dental procedure has been classified as cough inducing. In light of these observations the following additional considerations appear prudent in dental settings: Guidelines for Preventing the Transmission of Mycobacterium tuberculosis in Health-Care Facilities, MMWR; October 28, 1994 / 43(RR13);1-132 Risk of Occupational TB Transmission: Risk of Occupational TB Transmission Considered minimal Follow CDC/ADA guidelines No OSHA regulations (to date) Private Dental Offices Guidelines for Preventing the Transmission of Mycobacterium tuberculosis in Health-Care Facilities, MMWR; October 28, 1994 / 43(RR13);1-132 TB Guidelines: TB Guidelines During initial medical history and periodic updates DHCW should: Routinely ask all patients about a history of TB; And signs and symptoms suggestive of TB Guidelines for Preventing the Transmission of Mycobacterium tuberculosis in Health-Care Facilities, MMWR; October 28, 1994 / 43(RR13);1-132 TB Guidelines: TB Guidelines All elective dental care should be deferred until a physician determines: That the patient doesn’t have TB ; or Anti-TB therapy has been rendered and the patient is no longer infectious! Guidelines for Preventing the Transmission of Mycobacterium tuberculosis in Health-Care Facilities, MMWR; October 28, 1994 / 43(RR13);1-132 TB Guidelines: TB Guidelines Guidelines for Preventing the Transmission of Mycobacterium tuberculosis in Health-Care Facilities, MMWR; October 28, 1994 / 43(RR13);1-132 If urgent care must be provided for a patient with active TB or signs & symptoms suggestive of TB, TB isolation practices should be implemented DHCW should use appropriate respiratory protection while performing procedures on these patients Emergency Dental Treatment for TB Patients: Emergency Dental Treatment for TB Patients Perform treatment in facilities with TB isolation capability Use recommended respiratory protection Fit tested HEPA filter mask Select least invasive treatment options Accomplish definitive care after patient is no longer infectious Sputum Negative for Acid Fast Bacillus (AFB) Guidelines for Preventing the Transmission of Mycobacterium tuberculosis in Health-Care Facilities, MMWR; October 28, 1994 / 43(RR13);1-132 Tuberculosis: Tuberculosis Dental-care in “high risk” facilities Use engineering controls similar to those in general use areas of medical facilities with similar risk profile. Evaluation of Dental HCW TB symptoms Evaluate promptly Do not return to clinic until: TB Diagnosis is ruled out or; DHCW is on therapy and non-infectious Guidelines for Preventing the Transmission of Mycobacterium tuberculosis in Health-Care Facilities, MMWR; October 28, 1994 / 43(RR13);1-132 CDC/ADA Dental Office TB Recommendations: CDC/ADA Dental Office TB Recommendations Protocol for referring TB patients to dental isolation facility Protocol for identifying and referring patients for medical evaluation for TB DHCW education, training, counseling and screening Periodic risk assessment and updates Written Plan Should Include: Guidelines for Preventing the Transmission of Mycobacterium tuberculosis in Health-Care Facilities, MMWR; October 28, 1994 / 43(RR13);1-132 Slide134: Louis G. DePaola, DDS, MS (410) 706-7628 [email protected] I Questions?