Causes of death in the world from infectious disease

deaths per 100,000 people multiple cause of death main cause of death Deaths from infectious disease- US ( JAMA, 2000)

deaths per 100,000 people >65 y.o y.o. Deaths from infectious disease- US ( JAMA, 2000) ____ y.o y.o. 0-4 y.o.

Causes of death in the U.S. l CDC l 1. Cardiovascular disease l 2. Cancer l 3. Stroke l 4. Pneumonia- influenza( #7 in 1996) l >>15. AIDS ( #7. in 1997)

Emerging Infectious Diseases l Ebola virus > 50 deaths Oct l Hantavirus l Cryptosporidosis( Brewhouse tri) l E. coli and Enterococci l necrotizing Strep. A l Pneumococci l Staph. aureus

Emerging &Re-emerging Infectious Diseases l antimicrobial resistance l misuse of antibiotics l mobility- travel l food, water and agriculture l child care l Behaviors l hospitals-health care

Hepatitis C l formerly NANB l transmission similar to Hep B + often accompanies l 40-50% = chronic active hepatitis l acute liver disease; cirrhosis l ~ 90 % develop chronic carrier state l U.S. = 1992 ~ 150,000 infections l > 1.5 million infections in 1998 l >1000 HCW/yr. occupational! l hep-Ca > 11 % !!

Antimicrobial resistance l nosocomial infections >200,000/yr. l Vancomycin resistant Staph. Aureus l % l methacillin res.1999 >60% l inappropriate prescribing practices ! > 70 % !!

“Today’s discovery represents the triumph of modern science over a dreadful disease.” HEW Secretary Margaret Heckler 1983 upon the discovery of HTLV-III

AIDS EPIDEMIC December 2006 n 35 million HIV infections worldwide, > 6 million cumulative deaths worldwide, including > 1.3 million dead children, 830,000 infected children worldwide (4.5 million AIDS cases). n 60% of worldwide cases of HIV are in Africa (18 million, with 9 million cases of AIDS and 1.8 million AIDs deaths in Africa in 1998) In S. Africa 50% of hospital beds are for AIDS; estimated by 2010 that 9 countires in Africa will have their life expectancy drop 16 yrs.

HIV l 2006: 35 million, worldwide l 6 million deaths !! l infected women ( world) ~40 % l >1 million infected children ( 90% = 3rd world)

HIV l U.S.> 1.5 million l AIDS: U.S.>550,000 cases l AIDS: U.S.>350,000 deaths l changes in epidemiology l homosexual-bisexual males l IVDUs l women l children

HIV-AIDS in the U.S. l cases of AIDS-1996 =~ 56,000 l deaths from AIDS-1996 =~ 45,000 l cases of AIDS-2006=~ 25,000 l deaths from AIDS-2006 =~ 11,000

source: CDC cases per wk AIDS new cases Deaths alive with AIDS

Incubation Period to AIDS Cumulative % 0%3%12%36% 53% 68% 85% 1yr 3yr5yr8yr10yr 14yr 20yr

Viral Load Stage B

AIDS defining diseases* l Pneumoncytis pneumonia38% l HIV wasting syndrome**18% l Candidal esophagitis14% l Kaposi’s sarcoma10% l TB10% l lymphoma10% Viral: Herpesviridae, CMV, HPV, Pox family l Neurologic < AIDS-related pain (neuropathy, myelopathy) l ** loss of 10% body wt. < 30days

Clinical category C Bacterial infections, multiple or recurrent*Candidiasis, respiratory Candidiasis, esophagealCervical cancer ** CoccidioidomycosisCryptococcosis = CryptosporidiosisCytomegalovirus disease = Cytomegalovirus retinitisEncephalopathy, HIV related Herpes simplex = chronic; respiratory; esophageal Histoplasmosis = HIV encephalopathy HIV wasting syndromeImmunosuppression, severe HIV-related = IsosporiasisKaposi’s sarcoma = Lymphoid interstitial pneumonia*Lymphoma, Burkitt’s = Lymphoma, immunoblastic = Lymphoma, primary; brain M. avium complex = M. tuberculosis =, disseminated; extrapulmonary M. tuberculosis, pulmonary ** Mycobacterial disease Pneumocystis carinii pneumoniaPneumonia, recurrent ** Progressive multifocal leukoencephalopathySalmonella septicemia Toxoplasmosis * Not applicable as indicator of AIDS in adults/adolescents ** Not applicable as indicator of AIDS in children = Has oral manifestations

Dental patient management :AIDS l Opportunistic infections Pneumoncystis carinii pneumonia (PCP) Toxoplasmic encephalitis TB Mycobacterium avium complex(MAC) Streptococcal pneumonia CMV Candidiasis l Cancer

n Preferred Antiretroviral Regimens n Optimal: 2 NRTIs + PI; 2 NRTIs + NNRTI n Less desirable: 3 NRTIs n Unacceptable: monotherapy n Resistance 19901% 19947% % n Changing therapy: failure (rising viral load, falling CD4 count, symptoms, ADEs) never add a single drug to a failing regimen, begin with at least 2 drugs. Highly Active Antiretrovial Therapy (HAART)

Nucleoside RT Inhibitors - mg/day 30 day cost Nucleoside RT Inhibitors - mg/day 30 day cost Abacavir (ABC; Ziagen) 300 bid $ 349 Didanosine (ddI, Videx) 200 bid217 Lamivudine (3TC, Epivir) 150 bid259 Stavudine (d4T, Zerit) 40 bid274 Zalcitabine (ddC, Hivid) 0.75 tid212 Zidovudine (AZT, ZDV, Retrovir) 200 tid604 Zidovudiine + Lamivudine (Combivir) 1 tab bid 564 n Nucleotide RT Inhibitor - Adefovir 120 qdonly available thru EAP n Non-nucleoside RT inhibitors ( NNRTI) Delavirdine (Rescriptor) 400 tid239 Efavinrenz (EFV, Sustiva) 600 qd394 *Not drug of choice for HIV postexposure prohpylaxis Nevirapine (Viramune) * 200 bid279 *Not drug of choice for HIV postexposure prohpylaxis Anti-HIV Drugs

block an enzyme that cleaves Gag and Gag-Pol polyproteins Protease Inhibitors: block an enzyme that cleaves Gag and Gag-Pol polyproteins - 50 to 100X more potent than AZT Amprenavir (Agenerase) 50s, 150s1200 bid $ per month = 605 Indinavir (Crixivan) 800 q8h $ per month = 464 Nelfinavir (Viracept) 750 tid $ per month = 583 Ritonavir (Norvir) 600 tid $ per month = 668 Saquinavir (Invirase) 600 tid $ per month = 586 mg/day mg/day

Treatment of HIV Infection l Most untreated patients have HIV-1 RNA levels stabilize between ,000 copies/mL. In AIDS, levels > 1 million copies/mL l Combination therapy of NRTI + NNRTI + HIV Protease inhibitor l Up to 28% of newly infected individuals may contract HIV that is resistant to one or more anti-AIDS drugs HIV Therapy Edge is software to search gene sequences for over 120 drug resistance mutations and to report which drugs to avoid.

AIDS treatment l complex Rx : 1-8 months > $12, poor compliance HIV +ve & infectious viral genotyping to detect antiretroviral resistance l Opportuntistic infections CD-4 counts >500 ; esp. >200

Screening and rapid tests: Abbott/Murex Single Unit Diagnostic System [SUDS  ] HIV-1 test), oral mucosal transudate-based tests (e.g., OraSure  HIV-1 western blot kit), home test systems (e.g., Home Access  HIV-1 test kit).

Principles of medical management of dental patients l Detection l Physical Evaluation l Medical treatment l Status l Management

Management Considerations l Viral load will determine level of viremia, efficacy of antiretroviral therapy, disease progression, and prognosis, thus influencing appropriate treatment planning. There is no need for prophylactic medication prior to dental therapy based solely on viral load.

Management Considerations l Dental treatments, including extractions, can be safely performed in patients with platelet counts >50,000 platelets/mm 3. l Prophylactic bactericidal antibiotics need to be considered when the neutrophil count drops below 500 cells/mm 3 (normal 2,500-7,000 cells/mm 3 ), but at this stage the patient is often already medicated with antibiotics due to frequent bacterial infections and as prophylaxis against opportunistic infections.

There are very few complications associated with dental care of HIV-infected patients and most infected patients can be safely treated by general dental practitioners. Oral lesions found in HIV-infected persons are reliable markers for immune suppression, disease progression and AIDS.

GROUP 1 ORAL LESIONS Strongly Associated with HIV Infection l Candidiasis l Oral hairy leukoplakia l Kaposi’s sarcoma l Non-Hodgkin’s lymphoma l Periodontal disease - linear gingival erythema, necrotizing (ulcerative) gingivitis, necrotizing (ulcerative) periodontitis Oral candidiasis most common oral lesion among HIV+persons (39.6%), then hairy leukoplakia (26.3%), exfoliative cheilitis (18.3%), and linear gingival erythema (LGE) (11.5%). JOPM (4): in Thailand

Oral candidiasis in HIV l prevalent ( >45%) l related to other oral diseases( i.e. caries and periodontal disease, HSV, etc.) l proportional to low CD-4 counts l predictive of rapid progression to death

Oral Hairy Leukoplakia l Immunocompromised State l HIV+ / AIDS l Chemotherapy l Organ transplant l Autoimmune disease (SLE on prednisone 5-10mg/d X 1 yr + methotrexate) Often an indicator that AIDS will develop within a short time period

Human Papillomavirus l Condyloma acuminatum l Transmission l HPV DNA detected in sperm 32% of mendetected in 24 of 45 men hx or clinical evidence of HPV infection

HIV Infection l Angular cheilitis l Patient was HIV infected l Later was diagnosed with AIDS Erythematous candidiasis

Bacterial Infections l Systemic Infections l Oral Infections l Periodontal tissues l Necrotizing ulcerative gingivitis (NUG) l Linear gingival erythema l Necrotizing ulcerative periodontitis l Tongue and other mucosal structures

HIV Infection l Linear gingival erythemia

Necrotizing Ulcerative Periodontitis

HIV Infection l Recurrent herpes simplex infection in a patient with AIDS

HIV Infection l Herpes zoster l Out break occurred in patient with AIDS Harrison’s Online, hppt:// plate 11D-30, 2002

HIV Infection l Aphthous ulceration (major type) l Patient was diagnosed with AIDS

HIV Infection l Kaposi’s sarcoma

HIV transmission from HCW to patients l still only one case (Dr. Acer) ! l CDC : >70 infected HCW served over 100,000 patients tested = 0 HIV + l risk per million from HCW = l risk of death from PCN-ALLR= 20/million

HIV transmission from patients to HCW. l ~ 10 per year l dentistry: documented= 0possible= 7 l lab techs: documented= 18possible= 30 l nurses: documented= 15possible= 40 l MDs: documented= 0possible= 12 l others: documented= 10possible= 47 l Hep C> 1000 !!!

HIV transmission from patients to HCW. l NEEDLE STICKS ! avg. follow-up >$600 l wounds from HIV patients; l CDC: >4000 incidents < 10 seroconversions transmission rate= 0. 25% ( 1:400) l >70% from blood draws; >25 % IVs l >83% not high risk ( Rx goes in)... EPINet l 1999 California law

Management of Occupational Blood Exposures l Evaluate exposure source.Assess the risk of infection using available information. l Test known sources for HBsAg, anti-HCV, and HIV antibody (consider using rapid testing). l For unknown sources, assess risk of exposure to HBV, HCV, or HIV infection. l Do not test discarded needles or syringes for virus contamination. l Evaluate exposed person.Assess immune status for HBV infection (i.e., by history of HBV vaccination and vaccine response).

Management of Occupational Blood Exposures l Provide immediate care to the exposure site. Wash wounds and skin with soap and water. l Flush mucous membranes with water. l Reporting of exposure.Access to medical provider for testing. l Access to post-exposure protocol. l Documentation for workers compensation or disability claims. l Determine risk associated with exposure by: Type of fluid (e.g., blood, visibly bloody fluid, other potentially infectious fluid or tissue, and concentrated virus) and l Type of exposure (i.e., percutaneous injury, mucous membrane or nonintact skin exposure, and bites resulting in blood exposure.

l Mucous membrane exposures are assessed for type as either small volume (i.e., a few drops) or large volume (i.e., major blood splash) and the guidelines differ from those for percutaneous injuries in that basic 2-drug PEP is considered for small volume injuries from HIV-positive Class 1 source patients and basic 2-drug PEP is recommended for small volume injuries from HIV- positive Class 2 patients and large volume injuries from HIV-positive Class 1 patients. For skin exposures, follow- up is indicated only if there is evidence of compromised skin integrity (e.g., dermatitis, abrasion, or open wound).

Can you refuse to treat and HIV infected person? Federal law prohibits the dentist from refusing to treat patients with disabilities, including HIV infection. Under the Americans with Disabilities Act (AwDA), dental offices are considered places of public accommodation and are prohibited from refusing to treat patients with HIV solely because of their HIV status.