scabies, lice and hpv michael e. hagensee, m.d. ph.d. associate professor department of medicine...

SCABIES, LICE AND HPVSCABIES, LICE AND HPV

Michael E. Hagensee, M.D. Ph.D.Associate ProfessorDepartment of MedicineSection of Infectious DiseaseLSUHSC

DISCLOSUREDISCLOSURE I have no financial interests or other I have no financial interests or other

relationship with manufacturers of relationship with manufacturers of commercial products, suppliers of commercial products, suppliers of commercial services, or commercial commercial services, or commercial supporters. My presentation will not supporters. My presentation will not include any discussion of the include any discussion of the unlabeled use of a product or a unlabeled use of a product or a product under investigational use.product under investigational use.

STDs AND OTHER STDs AND OTHER GYNECOLOGIC INFECTIONSGYNECOLOGIC INFECTIONS

Objectives:

1. To be able to diagnose and treat scabies

2. To be able to diagnose and treat pubic lice

3. To know about the disease that HPV cause and how to treat/prevent them

SCABIESSCABIES

SCABIESSCABIES

SCABIESSCABIES

A. Etiology: Sarcoptes scabiei-human itch mite B. Epidemiology:

1. More than 100 million cases per year2. Itching due to excretions from burrowing mites3. Increase spread by close contact, crowding4. Medical practitioners are at high risk

 C. Clinical manifestations:

1. Itching increases at night and after a hot shower2. Burrows-dark wavy lines ending in small bleb3. Usual sites wrists, fingers, elbows and on penis4. Usually 15 mites per person

SCABIESSCABIES

SCABIESSCABIES

SCABIESSCABIES

5. Norwegian scabies: (crusted)

- thousands to millions of mites per person- seen only in immunosuppressed (HIV) individuals- erythema, thick keratotic crusts and dystrophic nails

 D. Diagnosis: Find mite of eggs in scraping vs empiric E. Treatment:

1. 5% permethrin cream2. 1% lindane (not in pregnant women) 3. Anti-pruritics as needed

LICELICE

LICELICE

A. Etiology:

1. Pediculus humanus var. capitis - head lice2. P. humanus var. corporis - clothing3. Pthirus pubic - pubic hair

 B. Epidemiology:

1. Lice feed on human blood once a day2. Saliva of lice produce an irritating rash3. Transmitted by close contact, shared combs, clothing

LICELICE

LICELICE

C. Clinical manifestations:

1. Intensely pruritic lesions2. 2-3 mm blue macules (maculae cerulae) at bite sites

 D. Diagnosis: Find nits or adult lice in hair or clothing E. Treatment:

1. 1% permethrin2. 0.5% malathion3. 1% lindane - more toxic and must apply a second dose 1 week later

- does not kill nits- not in pregnant women

4. Comb out nits after treatment

HUMAN PAPILLOMAVIRUS (HPV)(HPV)

• Papovavirus

• Most common viral STD

• ds DNA virus of 7.9 kB

• Entire DNA sequence is

known

HPV TYPESHPV TYPES

• 1,2 - plantar and

common warts

• 6,11 - condylomata and

laryngeal warts

• 16,18, and others -

anogenital malignancies

Defined by 10% difference in DNA sequence (L1 gene)Defined by 10% difference in DNA sequence (L1 gene)

METHODS TO DETECT HPV INFECTION

Clinical diagnosis: Genital wartsEpithelial defects

See cellular changes caused by the virus: Pap smear screening

Directly detect the virus: DNA hybridization or PCR*

Detect previous infection: (Research Only) Detection of antibody against HPV*

* Done in the Hagensee Laboratory

GENITAL WARTSGENITAL WARTS

GENITAL WARTSGENITAL WARTS

HPV EPIDEMIOLOGYHPV EPIDEMIOLOGYGENITAL WARTSGENITAL WARTS

• Usually caused by HPV 6 or 11

• Prevalence has increased 2-10x over past 30 years

• Most often found on penile shaft and anus in men,

vulva in women

• Spontaneous regression seen in 20% of cases

GENITAL WARTSGENITAL WARTS

GENITAL WARTSGENITAL WARTS

GENITAL HPV INFECTIONGENITAL HPV INFECTIONDIFFERENTIAL DIAGNOSISDIFFERENTIAL DIAGNOSIS

• CONDYLOMA LATUM-SYPHILIS

• MOLLUSCUM CONTAGIOSUM

• FIBROEPITHELIOMA AND OTHER CANCERS

• LICHEN PLANUS

• OTHER-HSV, LGV, CHANCROID,

GRANULOMA INGUINALE

GENITAL HPV INFECTIONGENITAL HPV INFECTIONTREATMENTTREATMENT

• OBSERVATION -20% spontaneous regression

• CRYOTHERAPY -70% cure rate

• PODOPHYLLIN/ TCA -30% cure rate

• SURGERY -laser-85% cure rate

• INTERFERON ALPHA -intralesional and systemic

• IMIQUIMOD -induces local interferon alpha production

• CIMETIDINE (Tagamet) – non-specific immune booster

HPV EPIDEMIOLOGYHPV EPIDEMIOLOGYANOGENITAL MALIGNANCYANOGENITAL MALIGNANCY

• Caused by high risk HPVs-16, 18, 31 and others

• Occurs mainly in older women-average age 54 years

• Associated with increased number of sexual partners,

smoking, and immune suppression

HPV IS ASSOCIATED WITHHPV IS ASSOCIATED WITH ANOGENITAL MALIGNANCIESANOGENITAL MALIGNANCIES

• HPV DNA is found in 50-98% of tumors depending

on location

• Oncogenic genes (E6 and E7) of high-risk types are

expressed in tumors

• E6 and E7 of high-risk types are oncogenic in-vitro

• Support from many epidemiologic studies

CERVICAL CANCERCERVICAL CANCER

CIN II

CERVICAL CANCER

2nd most common malignancy of women worldwide

More than 500,000 cases per year

# of cases declining in USA

Over 13,000cases in US in 1998

Over 35% mortality

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CERVIX - ANATOMY

CERVIX - ANATOMY

CERVIX - ANATOMY

COLLECTION OF A PAP SMEAR

CONVENTIONAL

NOW MOST CLINICS HAVE MOVED TO LIQUID-PAP SMEARS(Thin Prep, SurePath)

- preserve the morphology of the cells better

HPV DIAGNOSIS – PAP SMEARHPV DIAGNOSIS – PAP SMEARNormal, ASCUS – Atypical Squamous Cells of Unclear Significance

HPV PAP SMEARSHPV PAP SMEARSPap smear: Normal ASCUS – atypical cells of unclear significance:

repeat Pap vs test for HPV DNA LGSIL – low grade squamous intra-epithelial lesion:

colposcopy with biopsy HGSIL – high grade squamous intra-epithelial lesion:

colposcopy with biopsy and treat

Cervical biopsy: CIN I – mild dysplasia – usually spontaneously regresses CIN II – moderate dysplasia - treat CIN III – severe dysplasia – treat Carcinoma – in-situ – treat Invasive cervical cancer – treat

CERVICAL CANCER CERVICAL CANCER SCREENING METHODSSCREENING METHODS

HPV DNA Testing for questionable cases:

• Normal PAP smear - usual follow up

• ASCUS - may be cost-effective

• LGSIL - most regress

• HGSIL - refer for colposcopy and biopsy

CERVICAL CANCER CERVICAL CANCER SCREENING METHODSSCREENING METHODS

REFLEX TESTING USING HYBRID CAPTURE II

Collect a cervical swab for DNA testing from all women

and store them

Only those women with ASCUS (or LGSIL) – the swab is

sent for HPV DNA testing

HCII – positive for high-risk HPV – then refer to colposcopy

negative for high-risk HPV – then routine yearly screening

SCREENING METHODSSCREENING METHODS

CERVICAL CANCER CERVICAL CANCER SCREENING METHODSSCREENING METHODS

HIGH-RISK HPV INFECTIONHIGH-RISK HPV INFECTIONTREATMENTTREATMENT

• OBSERVATION

• CRYOTHERAPY-LASER

• CONE BIOPSY-SURGERY

• RETINOIDS??

PROPHYLACTIC VACCINES AGAINST HPV

Utilizing in-vitro capsid production: (VLPs – Virus-Like Particles)

Co-discovered by: Zhou et al, Virology 185:251, 1991 Kirnbauer et al, PNAS 89:12180, 1992

Hagensee et al, J. Virology 67:315, 1993

Particles made in the laboratory identical to in-vivo down to a resolution of 5 microns

No infectious potential

Can be made in vaccinia virus, baculovirus, yeast and bacterial expression systems

HPV VLPs

HPV capsids – EM and 3-D Reconstruction

PROPHYLACTIC VACCINES AGAINST HPV

COMPANYCOMPANY HPV TYPEHPV TYPE PHASEPHASE RESULTSRESULTS

MERCKMERCK 6,11,16,186,11,16,18 ApprovedApproved

GardasilGardasil

Serologic responseSerologic response

SafeSafe

MEDIMMUNEMEDIMMUNE

GSKGSK

16, 1816, 18 IIIIII Serologic responseSerologic response

SafeSafe

ACIP RecommendationsACIP Recommendations Routine vaccination with 3 doses of quadrivalent HPV vaccine for Routine vaccination with 3 doses of quadrivalent HPV vaccine for

females 11–12 years of age females 11–12 years of age – Can be started in females as young as 9 years of ageCan be started in females as young as 9 years of age

Catch-up vaccination for females 13Catch-up vaccination for females 13––26 years of age not previously 26 years of age not previously vaccinated or who have not completed the full vaccine seriesvaccinated or who have not completed the full vaccine series– Ideally, vaccine should be administered before potential exposure Ideally, vaccine should be administered before potential exposure

to HPV.to HPV. Each dose of quadrivalent HPV vaccine is 0.5 mL, administered Each dose of quadrivalent HPV vaccine is 0.5 mL, administered

intramuscularly.intramuscularly. Quadrivalent HPV vaccine is administered in a 3-dose schedule.Quadrivalent HPV vaccine is administered in a 3-dose schedule.

– The second and third doses should be administered 2 and 6 The second and third doses should be administered 2 and 6 months after the first dose.months after the first dose.

Quadrivalent HPV vaccine can be administered at the same visit Quadrivalent HPV vaccine can be administered at the same visit at which other age-appropriate vaccines are provided, such as Tdap, at which other age-appropriate vaccines are provided, such as Tdap, Td, and MCV4.*Td, and MCV4.*

Advisory Committee on Immunization Practices (ACIP). ACIP recommendations for the use of quadrivalent HPV vaccine. Available at: http://www.cdc.gov/nip/recs/provisional_recs/hpv.pdf. Accessed December 19, 2006.

*NOTE: Per the Prescribing Information, co-administration of GARDASIL with these vaccines has not been studied.

ACIP Recommendations ACIP Recommendations ((cont.cont.)) Current recommendations for cervical cancer screening have not Current recommendations for cervical cancer screening have not

changed for females who receive quadrivalent HPV vaccine.changed for females who receive quadrivalent HPV vaccine. Females who have an equivocal or abnormal Pap test, a positive Females who have an equivocal or abnormal Pap test, a positive

Hybrid Capture IIHybrid Capture II high-risk test, or genital warts can receive the high-risk test, or genital warts can receive the quadrivalent HPV vaccine.quadrivalent HPV vaccine.– Recipients should be advised that the vaccine will not have Recipients should be advised that the vaccine will not have

therapeutic effect on existing Pap test abnormalities, HPV therapeutic effect on existing Pap test abnormalities, HPV infection, or genital warts. Vaccination would provide protection infection, or genital warts. Vaccination would provide protection against infection with vaccine HPV types not already acquired.against infection with vaccine HPV types not already acquired.

Lactating women can receive quadrivalent HPV vaccine.Lactating women can receive quadrivalent HPV vaccine. Immunocompromised females can receive quadrivalent HPV vaccine.Immunocompromised females can receive quadrivalent HPV vaccine.

– However, the immune response to vaccination and vaccine However, the immune response to vaccination and vaccine effectiveness might be less than in females who are effectiveness might be less than in females who are immunocompetent.immunocompetent.

Quadrivalent HPV vaccine is contraindicated in people with a history of Quadrivalent HPV vaccine is contraindicated in people with a history of immediate hypersensitivity to yeast or to any vaccine component.immediate hypersensitivity to yeast or to any vaccine component.

ACIP. Recommendations for the use of quadrivalent HPV vaccine. Available at: http://www.cdc.gov/nip/recs/provisional_recs/hpv.pdf. Accessed December 19, 2006.

ACIP Recommendations ACIP Recommendations ((cont.cont.))

Quadrivalent HPV vaccine is not recommended Quadrivalent HPV vaccine is not recommended for use in pregnancy.for use in pregnancy.

Individuals should report any exposure to the Individuals should report any exposure to the vaccine during pregnancy to the vaccine vaccine during pregnancy to the vaccine pregnancy registry.pregnancy registry.

Quadrivalent HPV vaccine can be administered Quadrivalent HPV vaccine can be administered to females with minor acute illnesses.to females with minor acute illnesses.– Vaccination of people with moderate or severe acute Vaccination of people with moderate or severe acute

illnesses should be deferred until after the illness illnesses should be deferred until after the illness improves.improves.

ACIP. Recommendations for the use of quadrivalent HPV vaccine. Available at: http://www.cdc.gov/nip/recs/provisional_recs/hpv.pdf. Accessed December 19, 2006.