Chapter 17:Chapter 17:

Immunization and Immune TestingImmunization and Immune Testing

History of Vaccines• 1212thth Century: Century: Chinese developed variolation procedure to Chinese developed variolation procedure to

immunize young children from smallpox. Eventually practice immunize young children from smallpox. Eventually practice was outlawed in U.S. and England due to 1-2% death rate.was outlawed in U.S. and England due to 1-2% death rate.

• 1798: 1798: SmallpoxSmallpox vaccine (cowpox) results published by Jenner vaccine (cowpox) results published by Jenner• 1885: 1885: RabiesRabies vaccine developed by Pasteur vaccine developed by Pasteur• 1906: 1906: PertussisPertussis (whooping cough) vaccine developed (whooping cough) vaccine developed• 1928: 1928: DiphtheriaDiphtheria vaccine developed vaccine developed• 1933: 1933: TetanusTetanus toxoid vaccine developed toxoid vaccine developed• 1946: 1946: DPTDPT combination vaccine becomes available combination vaccine becomes available• 1955: 1955: PolioPolio inactivated vaccine (IPV) licensed by Salk inactivated vaccine (IPV) licensed by Salk• 1963: 1963: Polio oralPolio oral vaccine (OPV) developed by Sabin vaccine (OPV) developed by Sabin• 1963: 1963: MeaslesMeasles vaccine developed vaccine developed• 1968: 1968: MumpsMumps vaccine developed vaccine developed• 1969: 1969: Rubella/German measlesRubella/German measles vaccine developed vaccine developed• 1972: U.S. ended routine smallpox vaccination1972: U.S. ended routine smallpox vaccination

Effect of Immunization on Disease Incidence in U.S.

History of Vaccines• 1978: 1978: PneumococcalPneumococcal vaccine becomes available vaccine becomes available• 1979: 1979: MMRMMR combination vaccine added to routine childhood combination vaccine added to routine childhood

immunization schedule immunization schedule• 1987: 1987: Hemophilus influenzaeHemophilus influenzae type B (Hib) vaccine licensed type B (Hib) vaccine licensed• 1988: Vaccine Injury Compensation Program funded1988: Vaccine Injury Compensation Program funded• 1991: 1991: Hepatitis BHepatitis B recombinant vaccine recommended for recombinant vaccine recommended for

infants. Vaccine was licensed in 1986. infants. Vaccine was licensed in 1986.• 1995: 1995: VaricellaVaricella (chickenpox) vaccine licensed (chickenpox) vaccine licensed• 1996: 1996: DTaPDTaP (acellular Perstussis) vaccine licensed for (acellular Perstussis) vaccine licensed for

children under 18 mo.; believed to be safer than children under 18 mo.; believed to be safer than DTP. DTP.

• 1998: 1998: RotavirusRotavirus vaccine licensed for diarrheal disease vaccine licensed for diarrheal disease• 1999: 1999: RotavirusRotavirus vaccine vaccine removed for safety reasonsremoved for safety reasons• 2000: 2000: Polio oralPolio oral vaccine vaccine removed for safety reasonsremoved for safety reasons

PrevnarPrevnar (Pneumococcal conjugate vaccine) licensed (Pneumococcal conjugate vaccine) licensed

History of Vaccines

• 2002: Thimerasol use as vaccine preservative in most 2002: Thimerasol use as vaccine preservative in most pediatric vaccines pediatric vaccines discontinued due safety concernsdiscontinued due safety concerns

• 2002: 2002: FlumistFlumist (inhaled flu vaccine) approved by FDA (inhaled flu vaccine) approved by FDA• 2007:2007: Gardasil Gardasil (HPV) and (HPV) and MenactraMenactra (meningitis) vaccines (meningitis) vaccines

licensed licensed • 2010: Warning on Rotavirus vaccines contaminated with 2010: Warning on Rotavirus vaccines contaminated with

porcine (pig) virus.porcine (pig) virus.

VACCINE TYPES

I. Live attenuated vaccines: Mutant viral or bacterial strains produce an asymptomatic infection in host.

Examples: •Polio (oral, Sabin vaccine)

•Measles, Mumps and Rubella (MMR)

•Yellow fever

•Chickenpox

•Flu-Mist Influenza

• Advantages: Better immune response (cell-mediated), contact

immunity• Disadvantages: May cause disease due to contamination, genetic instability, residual virulence. Risks to fetus in pregnant women.Oral polio vaccine recently discontinued in U.S. due to polio cases.

II. Killed or inactivated vaccines:II. Killed or inactivated vaccines: Virus or bacterium is typically grown in eggs or cell Virus or bacterium is typically grown in eggs or cell

culture and inactivated with formalin.culture and inactivated with formalin.Examples:Examples:

Polio (shots, Salk vaccine)Polio (shots, Salk vaccine) RabiesRabies Pertussis (whooping cough)Pertussis (whooping cough) Influenza A & B (shots)Influenza A & B (shots)

Advantages: Advantages: Immunization with little or no risk of Immunization with little or no risk of infection.infection.

DisadvantagesDisadvantages: Less effective immune response : Less effective immune response (humoral), inactivation may alter viral antigens. (humoral), inactivation may alter viral antigens.

Typically require several boosters.Typically require several boosters.Toxic preservatives (formalin, thimerasol, etc.)Toxic preservatives (formalin, thimerasol, etc.)Adjuvants used to increase antigenicity (aluminum Adjuvants used to increase antigenicity (aluminum

phosphate, saponin, etc.) can cause local phosphate, saponin, etc.) can cause local inflamation.inflamation.

Flu Vaccine is Made from Eggs

III. Toxoid vaccines: III. Toxoid vaccines:

Bacterial toxin is chemically or thermally modified.Bacterial toxin is chemically or thermally modified.

Examples:Examples: Tetanus toxoidTetanus toxoid Diphteria toxoidDiphteria toxoid

Advantages: Advantages:

Immunization with little or no risk of infection.Immunization with little or no risk of infection.

DisadvantagesDisadvantages: :

Less effective immune response (humoral Less effective immune response (humoral immunity), inactivation may alter viral antigens. immunity), inactivation may alter viral antigens.

May require multiple boosters (e.g. every 10 years).May require multiple boosters (e.g. every 10 years).

IV. Recombinant vaccines:IV. Recombinant vaccines: Antigens from pathogen are produced by Antigens from pathogen are produced by

genetically engineered cells or viruses.genetically engineered cells or viruses.Examples: Examples:

Hepatitis BHepatitis B Blastomyces (fungus)Blastomyces (fungus) Experimental vaccines (Salmonella, herpesviruses, Experimental vaccines (Salmonella, herpesviruses,

adenoviruses, and poxviruses)adenoviruses, and poxviruses)

Advantages: Advantages: Little or no risk of infection.Little or no risk of infection.DisadvantagesDisadvantages: Less effective immune response.: Less effective immune response.

Examples of Recombinant Vaccines

Vaccine Safety ConcernsAdverse ReactionsAdverse Reactions: May occur almost immediately : May occur almost immediately or within days, weeks, or months of vaccination.or within days, weeks, or months of vaccination.1. Toxic Effects1. Toxic Effects: : • Bacterial ToxinsBacterial Toxins: Killed bacterial vaccines can release : Killed bacterial vaccines can release

toxins into the bloodstream. May be associated with toxins into the bloodstream. May be associated with swelling, soreness, fever, behavioral and neurological swelling, soreness, fever, behavioral and neurological problems (ADHD, autism, etc.).problems (ADHD, autism, etc.).

• Vaccine Ingredients:Vaccine Ingredients: May cause neurological, May cause neurological, immunological, digestive, or other problems.immunological, digestive, or other problems.

• ThimerosolThimerosol is a preservative used for multiple dose vaccines is a preservative used for multiple dose vaccines that contains 49% ethylmercury. Removed from most pediatirc that contains 49% ethylmercury. Removed from most pediatirc vaccines in 2002.vaccines in 2002.

• Other ingredientsOther ingredients: Aluminum, formaldehyde, benzethonium : Aluminum, formaldehyde, benzethonium chloride, ethylene glycol, glutamate, phenol, etc.chloride, ethylene glycol, glutamate, phenol, etc.

Vaccine Safety Concerns2. Immune Reactions2. Immune Reactions::

• AutoimmuneAutoimmune: Patient makes antibodies that cross : Patient makes antibodies that cross react with host antigens. May trigger:react with host antigens. May trigger:

• Rheumatoid arthritisRheumatoid arthritis• Juvenile diabetesJuvenile diabetes• Multiple sclerosisMultiple sclerosis• Crohn’s disease (bowel inflammation)Crohn’s disease (bowel inflammation)• Guillain-Barre syndrome (muscle weakness, paralysis), andGuillain-Barre syndrome (muscle weakness, paralysis), and• EncephalitisEncephalitis

Suspect vaccines include measles, tetanus, and influenza shots. Suspect vaccines include measles, tetanus, and influenza shots. • Allergic reactionsAllergic reactions: Vaccine ingredients may induce : Vaccine ingredients may induce

allergic reactions and/or anaphylactic shock in allergic reactions and/or anaphylactic shock in certain individuals. certain individuals. E.g.: Eggs, gelatin, neomycin, and streptomycin.E.g.: Eggs, gelatin, neomycin, and streptomycin.

Vaccine Safety Concerns3. Infectious Pathogens:3. Infectious Pathogens:

• Live attenuated virus vaccines can mutate back to a Live attenuated virus vaccines can mutate back to a harmful form and cause the disease they are harmful form and cause the disease they are designed to prevent: oral polio, measles, mumps, designed to prevent: oral polio, measles, mumps, rubella, and chickenpox vaccines.rubella, and chickenpox vaccines.

• Smallpox vaccine: About 1 in 1 million individuals will develop a Smallpox vaccine: About 1 in 1 million individuals will develop a fatal reaction to the vaccine.fatal reaction to the vaccine.

• Vaccines may be contaminated with other virusesVaccines may be contaminated with other viruses• Contaminiated Rotavirus vaccines in 2010Contaminiated Rotavirus vaccines in 2010

Vaccine Safety ConcernsCan Vaccines Cause Autism?Can Vaccines Cause Autism?

Modern EpidemicModern Epidemic: A 2009 report in : A 2009 report in Journal of Pediatrics Journal of Pediatrics indicates that one in 100 children in the United States are indicates that one in 100 children in the United States are autistic. In 1960s incidence was 1 in 2,000. Boys are more autistic. In 1960s incidence was 1 in 2,000. Boys are more heavily affected than girls (about 1 in 50 boys; 4-5 X higher heavily affected than girls (about 1 in 50 boys; 4-5 X higher rates of autism). Onset of symptoms usually occurs between 1 rates of autism). Onset of symptoms usually occurs between 1 and 3 years of age.and 3 years of age.

Symptoms in Three AreasSymptoms in Three Areas: Can vary from severe to mild.: Can vary from severe to mild.• Communication:Communication: Loss of language, language delays, poor Loss of language, language delays, poor

expressive and receptive languageexpressive and receptive language• Repetitive behaviors: Repetitive behaviors: Stimming, hand flapping, running in Stimming, hand flapping, running in

circles, rocking, obsessions with certain thingscircles, rocking, obsessions with certain things• Social Difficulties: Social Difficulties: Poor eye contact, isolation, aggression, Poor eye contact, isolation, aggression,

lack of social skills, tantrumslack of social skills, tantrums

Vaccine Safety ConcernsCan Vaccines Cause Autism?Can Vaccines Cause Autism?

CauseCause: Unknown. Traditional treatment focuses on : Unknown. Traditional treatment focuses on symptoms: speech, occupational and behavioral symptoms: speech, occupational and behavioral therapy.therapy.

Biomedical HypothesisBiomedical Hypothesis::• Risk factors: Risk factors: Genetic predisposition, C-section birth, older Genetic predisposition, C-section birth, older

parents, family history of autoimmune diseases, exposure to parents, family history of autoimmune diseases, exposure to toxic chemicals (pesticides, lead, mercury, etc). toxic chemicals (pesticides, lead, mercury, etc).

• Multiple vaccines and toxins at early age overwhelm Multiple vaccines and toxins at early age overwhelm immune system of susceptible individuals. immune system of susceptible individuals.

• Impaired immunity: May result in persistent infections. Impaired immunity: May result in persistent infections. Frequent ear infections, colds, etc.Frequent ear infections, colds, etc.

• Repeated use of antibiotics to treat infections may wipe out Repeated use of antibiotics to treat infections may wipe out beneficial microbial flora and allow “bad microbes” (yeasts beneficial microbial flora and allow “bad microbes” (yeasts and others) to overgrow (and others) to overgrow (gut dysbiosisgut dysbiosis) further impairing ) further impairing immune system and health.immune system and health.

Vaccine Safety ConcernsCan Vaccines Cause Autism?Can Vaccines Cause Autism?

Biomedical HypothesisBiomedical Hypothesis: Common related issues: Common related issues Digestive problems: Digestive problems: Inability to digest and absorb certain Inability to digest and absorb certain

foods (milk, gluten, and others). May develop multiple food foods (milk, gluten, and others). May develop multiple food intolerances and allergies.intolerances and allergies.

Neurological symptoms: Neurological symptoms: May be caused by gut dysbiosis May be caused by gut dysbiosis (microbial toxins) and digestive problems (caseomorphin, (microbial toxins) and digestive problems (caseomorphin, gliadorphin).gliadorphin).

Alternative biomedical therapiesAlternative biomedical therapies: : • Special diet (Gluten/Casein free and others)Special diet (Gluten/Casein free and others)• Gut health: Probiotics, prebiotics, antifungals, and othersGut health: Probiotics, prebiotics, antifungals, and others• Nutritional supplementsNutritional supplements• DetoxificationDetoxification• Consider revised vaccine scheduleConsider revised vaccine schedule

Immune TestingImmune TestingLabelled Antibody Tests: Labelled Antibody Tests: Use modified antibodies Use modified antibodies

to detect specific proteins or antibodies.to detect specific proteins or antibodies.1. ELISA (Enzyme Linked Immuno Sorbent Assay)1. ELISA (Enzyme Linked Immuno Sorbent Assay)

Can detect the presence of antibodies or Can detect the presence of antibodies or antigens antigens Used for HIV testing and many other diseasesUsed for HIV testing and many other diseases

Can quantify amounts of antigens or Can quantify amounts of antigens or antibodiesantibodies

Easy to perform, inexpensive, and quickEasy to perform, inexpensive, and quick First line test, easily automatedFirst line test, easily automated Disadvantage: Disadvantage: False positive results are not False positive results are not

uncommonuncommon

Enzyme Linked Immunosorbent Assay (ELISA)

Enzyme Linked Immunosorbent Assay (ELISA)

Immune TestingImmune TestingLabelled Antibody Tests: Labelled Antibody Tests: Use modified antibodies Use modified antibodies

to detect specific proteins or antibodies.to detect specific proteins or antibodies.2. Western Blot Test:2. Western Blot Test:

More expensive, time consuming, and difficult to More expensive, time consuming, and difficult to performperform

Used as a confirmatory test after a positive ELISAUsed as a confirmatory test after a positive ELISA Can detect different types of antibodies or proteinsCan detect different types of antibodies or proteins Less subject to misinterpretationLess subject to misinterpretation Three steps: Three steps:

1.1. ElectrophoresisElectrophoresis2.2. BlottingBlotting3.3. ELISAELISA

Western Blotting

Immune TestingImmune TestingLabelled Antibody Tests: Labelled Antibody Tests: Use modified antibodies Use modified antibodies

to detect specific proteins or antibodies.to detect specific proteins or antibodies.3. Fluorescent Antibody Tests 3. Fluorescent Antibody Tests

Direct fluorescence: Identifies antigen in a Direct fluorescence: Identifies antigen in a tissue tissue M. tuberculosis in sputumM. tuberculosis in sputum Viruses in tissuesViruses in tissues

Indirect Fluorescence: Can identify antigens in Indirect Fluorescence: Can identify antigens in tissue as well as antibodies in an individual’s tissue as well as antibodies in an individual’s serumserum

Indirect Fluorescent Antibody Test

Chapter 13 (Extra Material):Chapter 13 (Extra Material):

HerpesvirusesHerpesviruses

HerpesvirusesHerpesvirusesFamily of over 100 viruses which infect a broad range of Family of over 100 viruses which infect a broad range of

animals.animals.

Polyhedral capsid:Polyhedral capsid: Icosahedral capsid, 100-110 nm in Icosahedral capsid, 100-110 nm in

diameter. diameter.

Envelope: Envelope: Contains viral glycoproteins on its surface. Contains viral glycoproteins on its surface.

Virion is about 200 nm in diameter.Virion is about 200 nm in diameter.

Tegument: Tegument: Unique to herpesviruses. Amorphous Unique to herpesviruses. Amorphous

material surrounding capsid. Contains several viral material surrounding capsid. Contains several viral

proteins.proteins.

Large genome:Large genome: 140-225 kb of linear dsDNA which 140-225 kb of linear dsDNA which

circularizes after infection.circularizes after infection.

Biological Properties of HerpesvirusesBiological Properties of Herpesviruses Encode large array of enzymes involved in Encode large array of enzymes involved in

nucleic acid metabolism.nucleic acid metabolism. Synthesis of viral DNA and assembly of capsid Synthesis of viral DNA and assembly of capsid

occurs in the nucleus.occurs in the nucleus. Production of infectious progeny causes Production of infectious progeny causes

destruction of infected cell.destruction of infected cell. Latency:Latency: Can remain latent in their natural Can remain latent in their natural

hosts. Viral DNA remains as closed circular hosts. Viral DNA remains as closed circular molecule and only a few viral genes are molecule and only a few viral genes are expressed.expressed.

Establish Establish life-long infectionslife-long infections..

Human HerpesvirusesHuman HerpesvirusesVirusVirus Common Name/DiseaseCommon Name/Disease ClassClass SizeSize LatencyLatency

HHV-1HHV-1 Herpes simplex 1 (HSV-1)Herpes simplex 1 (HSV-1) 150 kb150 kb SensorySensory

Oral, ocular lesions, encephalitisOral, ocular lesions, encephalitis nerve ganglianerve ganglia

HHV-2HHV-2 Herpes simplex 2 (HSV-2)Herpes simplex 2 (HSV-2) 150 kb150 kb SensorySensory

Genital lesions, neonatal infectionsGenital lesions, neonatal infections nerve ganglianerve ganglia

HHV-3HHV-3 Varicella zoster virusVaricella zoster virus 130 kb130 kb SensorySensory

Chickenpox, shinglesChickenpox, shingles nerve ganglianerve ganglia

HHV-4HHV-4 Epstein-Barr virusEpstein-Barr virus 170 kb170 kb B cellsB cells

Mononucleosis, tumors`Mononucleosis, tumors` Salivary glandSalivary gland

HHV-5 HHV-5 Human CytomegalovirusHuman Cytomegalovirus 230 kb230 kb LymphocytesLymphocytes

Microcephaly, infections in Microcephaly, infections in

immunocompromised hostsimmunocompromised hosts

HHV-6/7HHV-6/7 Human Herpesvirus 6/7Human Herpesvirus 6/7 160 kb160 kb CD4 T cellsCD4 T cells

Roseola InfantumRoseola Infantum

HHV-8HHV-8 Human Herpesvirus 8Human Herpesvirus 8 140 kb140 kb Kaposi’s Kaposi’s

Kaposi’s sarcoma, lymphoma?Kaposi’s sarcoma, lymphoma? Sarcoma tissue Sarcoma tissue

Clinical Manifestations of HSV-1Clinical Manifestations of HSV-1EpidemiologyEpidemiology: 70-90% of adults are : 70-90% of adults are

infected. Most are asymptomatic.infected. Most are asymptomatic. Gingivostomatitis: Gingivostomatitis: Most common manifestation Most common manifestation

of primary HSV-1 infection. Initial infection of primary HSV-1 infection. Initial infection typically occurs in early childhood.typically occurs in early childhood.

Recurrent herpes labialis: Recurrent herpes labialis: Cold sores, fever Cold sores, fever blisters. After primary disease, virus remains blisters. After primary disease, virus remains latent in trigeminal ganglion. During latent in trigeminal ganglion. During reactivation, virus travels down nerve to reactivation, virus travels down nerve to peripheral location to cause recurrence.peripheral location to cause recurrence.

Whitlow: Whitlow: Infection of finger.Infection of finger.

Recurrent Herpes Labialis

Less than 1 day witherythema and burning

Same patient 24 h later with multiplefluid filled vesicles and erythema

Recurrent Herpes Labialis: Bilateral vesicles on upper and lower lips.Source: Atlas of Clinical Oral Pathology, 1999.

Herpetic Whitlow: Multiple crusting ulcerations that begin as vesicles.Source: Atlas of Clinical Oral Pathology, 1999.

Keratoconjunctivitis:Keratoconjunctivitis: Most common cause of Most common cause of corneal blindness in US.corneal blindness in US.

Eczema herpeticum: Eczema herpeticum: Severe herpetic outbreaks Severe herpetic outbreaks in areas with eczema.in areas with eczema.

Herpes gladiatorum:Herpes gladiatorum: Inoculation of abraded Inoculation of abraded skin by contact with infected secretions.skin by contact with infected secretions.

HSV encephalitis:HSV encephalitis: Most common cause of acute Most common cause of acute sporadic encephalitis in US.sporadic encephalitis in US.

Chronic herpes simplex infection:Chronic herpes simplex infection: Lesions in Lesions in atypical oral locations. Immunocompromised atypical oral locations. Immunocompromised patients.patients.

Chronic Herpes Simplex infection with lesions on tongue and lips.Source: Atlas of Clinical Oral Pathology, 1999.

Clinical Manifestations of HSV-2Clinical Manifestations of HSV-2EpidemiologyEpidemiology: Acquisition follows typical pattern : Acquisition follows typical pattern

of STD. Seroprevalence ranges from 10% to of STD. Seroprevalence ranges from 10% to 80% Most individuals are asymptomatic.80% Most individuals are asymptomatic.

Genital Herpes: Genital Herpes: Most common manifestation HSV-2 Most common manifestation HSV-2 infection. infection. Most common cause of genital ulcers in U.S.Most common cause of genital ulcers in U.S.Lesions on cervix, perineum, or penis shaft.Lesions on cervix, perineum, or penis shaft.Recurrence rates vary widely.Recurrence rates vary widely.

Perirectal HerpesPerirectal Herpes: Can be severe in AIDS patients.: Can be severe in AIDS patients.

Orofacial herpes:Orofacial herpes: Less than 5% of cases. Less than 5% of cases. Neonatal HerpesNeonatal Herpes: Due to contact with infected genital : Due to contact with infected genital

secretions during delivery. Severe disease with secretions during delivery. Severe disease with encephalitis, pneumonitis, hepatitis, and retinitis.encephalitis, pneumonitis, hepatitis, and retinitis.

Herpes simplex 2 infection with fluid filled vesicles on penis.Source: Mike Remington, University of Washington Viral Disease Clinic

Genital Herpes

Acyclovir resistant peri-rectal HSV2 infection in HIV infected male.Source: AIDS, 1997

Clinical Manifestations of Varicella Clinical Manifestations of Varicella Zoster (HHV-3)Zoster (HHV-3)

Chickenpox (Varicella): Chickenpox (Varicella): Most common manifestation of Most common manifestation of primary herpes zoster infection.primary herpes zoster infection.EpidemiologyEpidemiology: Highly communicable. Airborne or skin : Highly communicable. Airborne or skin transmission.transmission. Incubation period 14 days. Incubation period 14 days. Before the vaccine (Varivax) was introduced in 1995, Before the vaccine (Varivax) was introduced in 1995, there were about 3 million cases/year in US (most in the there were about 3 million cases/year in US (most in the spring). Since 1995, the number of cases has dropped by spring). Since 1995, the number of cases has dropped by 85%. 85%. SymptomsSymptoms: Malaise, sore throat, rhinitis, and generalized : Malaise, sore throat, rhinitis, and generalized rash that progresses from macules to vesicles. Intraoral rash that progresses from macules to vesicles. Intraoral lesions may precede rash.lesions may precede rash.ComplicationsComplications: Reye’s syndrome, bacterial : Reye’s syndrome, bacterial superinfection of lesions, varicella pneumonia and superinfection of lesions, varicella pneumonia and neonatal varicella (30% mortality).neonatal varicella (30% mortality).

Chickenpox and Shingles are Caused by Varicella Zoster

Clinical Manifestations of Varicella Clinical Manifestations of Varicella Zoster (HHV-3)Zoster (HHV-3)

VaccineVaccine: Prevents chickenpox in 70-90% of recipients. : Prevents chickenpox in 70-90% of recipients. First dose given between 12 and 18 months, second dose First dose given between 12 and 18 months, second dose at 4 to 6 years. May help prevent shingles in adults. at 4 to 6 years. May help prevent shingles in adults. Adults get two shots 4 to 8 weeks apart.Adults get two shots 4 to 8 weeks apart.

Shingles (Herpes Zoster): Shingles (Herpes Zoster): Recurrence of latentRecurrence of latent herpes herpes zoster infection.zoster infection.EpidemiologyEpidemiology: Occurs in 10-20% of individuals who : Occurs in 10-20% of individuals who have has chickenpox at some stage of life. Incidence have has chickenpox at some stage of life. Incidence increases with old age, impaired immunity, alcohol abuse, increases with old age, impaired immunity, alcohol abuse, and presence of malignancy. and presence of malignancy. SymptomsSymptoms: Vesicular eruption on skin or mucosa, that : Vesicular eruption on skin or mucosa, that follows pathway of nerves. Typically unilateral, stopping follows pathway of nerves. Typically unilateral, stopping at midline.at midline.ComplicationsComplications: Post-herpetic neuralgia can last months : Post-herpetic neuralgia can last months to years.to years.

EBV Associated Diseases (HHV-4)EBV Associated Diseases (HHV-4)EpidemiologyEpidemiology: 90% of adults are infected. : 90% of adults are infected.

Initial infection typically occurs in early Initial infection typically occurs in early childhood or adolescence.childhood or adolescence.

Most individuals are asymptomatic, but shed Most individuals are asymptomatic, but shed

virus in saliva throughout life.virus in saliva throughout life. Infectious mononucleosis:Infectious mononucleosis: A minority of infected A minority of infected

individuals. Fever, pharyngitis, and individuals. Fever, pharyngitis, and lymphadenopathy. Splenomegaly is common.lymphadenopathy. Splenomegaly is common.

Endemic Burkitt’s Lymphoma (Africa)Endemic Burkitt’s Lymphoma (Africa) Nasopharyngeal carcinoma (Asia)Nasopharyngeal carcinoma (Asia) Oral Hairy Leukoplakia:Oral Hairy Leukoplakia: In HIV + individuals. In HIV + individuals.

Diseases Associated with Epstein Barr Virus

Oral Hairy Leukoplakia with bilateral thickening of the tongue.Source: AIDS, 1997.

Diseases Associated with Epstein Barr Virus

Non-Hodgkin’s Lymphoma:Non-Hodgkin’s Lymphoma: In HIV + In HIV + individualsindividuals

Hodgkin’s Lymphoma:Hodgkin’s Lymphoma: 50% of cases. 50% of cases. Smooth muscle tumor (children)Smooth muscle tumor (children) Thymic lymphoepitheliomaThymic lymphoepithelioma Salivary gland carcinomaSalivary gland carcinoma Urogenital carcinomaUrogenital carcinoma

Clinical Manifestations of Clinical Manifestations of Cytomegalovirus (HHV-5)Cytomegalovirus (HHV-5)

EpidemiologyEpidemiology: 50% of US population is seropositive.: 50% of US population is seropositive.

TransmissionTransmission: Perinatal, early childhood, sexual, : Perinatal, early childhood, sexual, transfusions, and organ transplants.transfusions, and organ transplants.

SymptomsSymptoms: Most cases are asymptomatic.: Most cases are asymptomatic. Congenital CMV: May cause intellectual or hearing Congenital CMV: May cause intellectual or hearing

deficits.deficits. Pneumonitis in bone marrow transplants.Pneumonitis in bone marrow transplants. Retinitis, esophagitis, and colitis are common in AIDS Retinitis, esophagitis, and colitis are common in AIDS

patientspatients

HHV-8 Associated DiseasesHHV-8 Associated Diseases First identified in 1995. First identified in 1995. Kaposi’s SarcomaKaposi’s Sarcoma: Accounts for 80% of all : Accounts for 80% of all

cancers in AIDS patients.cancers in AIDS patients.

Lesions are flat or raised areas of red to purple to Lesions are flat or raised areas of red to purple to

brown discolorationbrown discoloration. . May be confused with May be confused with hemangioma or hematoma.hemangioma or hematoma. Strong male predominance.Strong male predominance. 2/3 of affected patients present oral lesions2/3 of affected patients present oral lesions Oral lesions are initial presentation in 20% of patients.Oral lesions are initial presentation in 20% of patients. Progressive malignancy that may disseminate widely.Progressive malignancy that may disseminate widely. Oral lesions are a major source of morbidity and Oral lesions are a major source of morbidity and

frequently require local therapy.frequently require local therapy.

Extensive symmetric tumor lesions of Kaposis’s sarcoma in an AIDS patient.Source: AIDS, 1997

Kaposi’s Sarcoma hemorrhagic mass on anterior maxillary gingiva.Source: Atlas of Clinical Oral Pathology, 1999.

Endemic Kaposi’s Sarcoma, nodular form.Source: AIDS, 1997.