listened Comprehensive Guide to Vaccines for Varicella, Zoster, HPV, and MPox

Varicella Zoster Virus (VZV) Pathophysiology and Infections

• General Characteristics of VZV:     * Member of the herpesvirus family.     * Possesses the ability to lay dormant in the body after initial infection.

• Transmission and Entry:     * VZV enters the body through the respiratory tract and the conjunctiva.     * Incubation Period: Typically ranges from $14$ to $16$ days.

• Disease Manifestations:     * Primary Infection: Clinically known as Chickenpox.     * Secondary Infection: Clinically known as Shingles (Herpes Zoster).

Postherpetic Neuralgia (PHN)

• Definition: PHN is defined as the persistence of pain for $90$ days (or more) after the initial onset of the zoster rash.

• Epidemiology and Risk:     * Common complication of herpes zoster infection.     * Incidence rate is estimated between $10\%$ and $33\%$.     * The risk and incidence of PHN increase proportionally with age.

• Clinical Presentation:     * The pain is often debilitating to the patient.     * Duration of pain can last from several months to many years.

• Management Limitations:     * Antiviral medications can effectively shorten the duration of the physical lesion (rash).     * Antivirals CANNOT prevent or treat PHN once it occurs.

• Treatment Options for PHN Pain:     * Gabapentin.     * Oxcarbazepine.

Varicella Vaccination (Varivax)

• Primary Indication: For the prevention of chickenpox.

• Vaccine Type: Live attenuated vaccine.

• Administration: Subcutaneous (SQ) injection.

• Storage and Preparation:     * Supplied as a powder for reconstitution.     * The powder component must be stored frozen.

• Age Approval: Approved for use in individuals aged $12$ months and older.

• ACIP Dosing Schedule:     * The recommendation is a $2$-dose series.     * First Dose: Administered at $12$ to $15$ months of age.     * Second Dose: Administered at $4$ to $6$ years of age.

• Combination Products: Also available as part of the MMRV combination vaccine (ProQuad), which includes Measles, Mumps, and Rubella.

Shingles Vaccination (Shingrix)

• Vaccine Specifics:     * Trade Name: Shingrix®.     * Type: Recombinant Zoster Vaccine (RZV).     * Route: Intramuscular (IM) injection.

• Schedule:     * $2$-dose series.     * The second dose is given $2$ to $6$ months after the first dose.

• Approved Populations:     * Routine vaccination for persons aged $50$ years and older.     * Persons aged $19$ years and older with immunocompromised conditions.

• Adverse Reactions:     * Pain at the injection site.     * Myalgias (muscle pain).     * Fatigue.     * Headache.

Comparison: Shingrix (RZV) vs. Zostavax (ZVL)

• Status: Zostavax (Zoster Vaccine Live) is no longer available in the United States as of November $2020$.

• Vaccine Efficacy (VE) against Shingles:     * Shingrix (RZV):         * Age $50-59$ years: $96.6\%$         * Age $60-69$ years: $97.4\%$         * Age $\ge 70$ years: $91.3\%$     * Zostavax (ZVL) - Historical:         * Age $50-59$ years: $70\%$         * Age $60-69$ years: $64\%$         * Age $\ge 70$ years: $38\%$

• Vaccine Efficacy (VE) against Postherpetic Neuralgia (PHN):     * Shingrix (RZV):         * Age $\ge 50$ years: $91.2\%$         * Age $\ge 70$ years: $88.8\%$     * Zostavax (ZVL) - Historical:         * Age $60-69$ years: $64\%$         * Age $\ge 70$ years: $38\%$

• Duration of Effect:     * Shingrix (RZV): Projected duration of approximately $19$ years.     * Zostavax (ZVL): Range of $4-12$ years, depending on the age at the time of vaccination.

ACIP Recommendations for Shingrix (RZV)

• General Adult Population: RZV is recommended for all immunocompetent adults $\ge 50$ years old.     * This applies regardless of a past history of shingles or chickenpox.     * This applies regardless of whether the patient previously received the Zostavax (ZVL) vaccine.

• Immunocompromised Patients: Recommended for patients age $\ge 18$ years who are immunocompromised due to disease or medications.

• Dosing Interval Details:     * Standard: Second dose $2$ to $6$ months after the first.     * Accelerated: The second dose can be given $1$ to $2$ months after the first if the patient would benefit from a shorter time frame (e.g., immunocompromised patients).     * Delays: If $6$ months have elapsed since the first dose, the second dose should be administered as soon as possible. There is no need to restart the series.

Human Papillomavirus (HPV) Epidemiology

• Classification: Group of over $200$ subtypes.

• Clinical Range: Causes various conditions from regular skin warts to genital warts and several types of cancer.

• U.S. Burden:     * The most common sexually transmitted infection (STI) in the United States.     * Estimated $6.2$ million new cases occur every year.     * Up to $85\%$ of all persons will acquire HPV in their lifetime.     * Natural History: $90\%$ of cases "clear" (become undetectable by the immune system) within $2$ years.

• Oncogenic Potential:     * HPV is the primary cause of cervical cancer.     * Cervical cancer is the second most common cause of cancer death in women.     * There are approximately $12,000$ cases of cervical cancer in the US annually; approximately $90\%$ are attributed to HPV.

STI Prevalence and Incidence Statistics in the US

• Definitions:     * Prevalence: The estimated number of infections—both new and existing—in a given time period.     * Incidence: The estimated number of new infections diagnosed or undiagnosed.

• Prevalence and Incidence Data (Per-Disease):     * HPV: Prevalence estimated at $42.5$ million; annual incidence estimated at $13$ million.     * HSV-2 (Ages 14 and older): Prevalence $18.6$ million; incidence $572,000$.     * Trichomoniasis: Prevalence $6.9$ million; incidence $2.6$ million.     * Chlamydia: Prevalence $4$ million; incidence $2.4$ million.     * HIV (Ages 13 and older): Prevalence $984,000$ (sexually acquired data); incidence $32,600$.     * Gonorrhea: Prevalence $209,000$; incidence $1.6$ million.     * Syphilis: Prevalence $156,000$; incidence $146,000$.     * HBV (Ages unavailable): Prevalence $103,000$ (sexually acquired data); incidence $8,300$.

Cancer Attenuation and HPV

• Percentage of Cancers Attributed to HPV:     * Anal Cancer: $91\%$     * Cervical Cancer: $91\%$     * Vaginal Cancer: $75\%$     * Oropharyngeal Cancer: $72\%$     * Vulvar Cancer: $69\%$     * Penile Cancer: $63\%$

HPV Prevention and Vaccination (Gardasil 9)

• Treatment Status: There is currently no treatment available for the HPV virus itself; management relies on clearing on its own or treating clinical symptoms.

• Gardasil®9:     * Type: Recombinant vaccine.     * Risk: There is no risk of developing HPV from the vaccine.     * Available Products: Gardasil®9 is the only HPV vaccine currently available in the US. Gardasil®4 (quadrivalent) and Cervarix® (bivalent) are no longer available.

HPV Vaccine Product Comparison

• Gardasil 9® (9-Valent):     * Serotypes: $6, 11, 16, 18, 31, 33, 45, 52, 58$.     * Administration: IM.     * Doses: $2$ or $3$.     * Ages: Females $9-45$ years; Males $9-45$ years.

• Gardasil® (Quadrivalent - Discontinued):     * Serotypes: $6, 11, 16, 18$.     * Ages: Females $9-26$ years; Males $9-26$ years.

• Cervarix® (Bivalent - Discontinued):     * Serotypes: $16, 18$.     * Ages: Females $10-25$ years; Males: No.

HPV Vaccination Clinical Considerations

• ACIP Recommendations:     * Target: All adults up to age $26$.     * Standard recommendation: At the $11$ to $12$-year-old physical examination.     * Early administration: Can be started as early as age $9$.     * Adults aged $27$ to $45$ years: Based on shared clinical decision-making between the patient and provider.     * Pregnancy: Not approved for use during pregnancy.

• Dose Numbers:     * Initiation before 15th birthday: $2$-dose series. The second dose is given $6$ to $12$ months after the first.     * Initiation after 15th birthday: $3$-dose series. Schedule is Baseline ($0$ months), $1-2$ months later, and $6$ months from the start.     * Note on Single Dose: The CDC has suggested recommendation for only one dose; however, this specific approach has not yet been studied and differs from AAP and AAFP recommendations.

• Clinical Rationale:     * Vaccination is best started before an individual is sexually active to provide maximum protection.     * Younger patients likely mount a higher immune response.     * The vaccine is prophylactic and will not "treat" an existing HPV infection.     * Patients already diagnosed with HPV should still receive the vaccine because they are often only infected with one type; the vaccine protects against the remaining covered subtypes.     * The vaccine does not protect against other STIs.

Injection Site Reaction Data (9-Valent HPV Vaccine)

• Females (Age 9-26):     * Pain: HPV9 ($83.9\%$), AAHS Control ($75.4\%$), Placebo ($48.6\%$)     * Swelling: HPV9 ($25.4\%$), AAHS Control ($15.8\%$), Placebo ($7.3\%$)     * Erythema (Redness): HPV9 ($24.7\%$), AAHS Control ($18.4\%$), Placebo ($12.1\%$)     * Pruritus (Itching): HPV9 ($3.2\%$), AAHS Control ($2.8\%$), Placebo ($0.6\%$)     * Bruising: HPV9 ($2.8\%$), AAHS Control ($3.2\%$), Placebo ($1.6\%$)

• Males (Age 9-26):     * Pain: HPV9 ($61.4\%$), AAHS Control ($50.8\%$), Placebo ($41.6\%$)     * Erythema: HPV9 ($16.7\%$), AAHS Control ($14.1\%$), Placebo ($14.5\%$)     * Swelling: HPV9 ($13.9\%$), AAHS Control ($9.6\%$), Placebo ($8.2\%$)     * Hematoma: HPV9 ($1\%$), AAHS Control ($0.3\%$), Placebo ($8.2\%$)

• Abbreviations: AAHS denotes amorphous aluminum hydroxyphosphate sulfate; Placebo denotes saline.

HPV Vaccine Effectiveness: Girls and Women (Ages 16-26)

• Data regarding serotypes $6, 11, 16, 18$:     * HPV 16- or 18-related CIN 2/3 or AIS: Efficacy $98.2\%$     * HPV 16- or 18-related VIN 2/3: Efficacy $100\%$     * HPV 16- or 18-related VaIN 2/3: Efficacy $100\%$     * HPV 6-, 11-, 16-, or 18-related CIN (CIN 1, CIN 2/3) or AIS: Efficacy $96\%$     * HPV 6-, 11-, 16-, or 18-related Genital Warts: Efficacy $99\%$     * HPV 6- and 11-related Genital Warts: Efficacy $99\%$

• Terminology: CIN: Cervical Intraepithelial Neoplasia; AIS: adenocarcinoma in situ; VIN: Vulvar Intraepithelial Neoplasia; VaIN: Vaginal Intraepithelial Neoplasia.

HPV Vaccine Effectiveness: Boys and Men (Ages 16-26)

• Data regarding serotypes $6, 11, 16, 18$:     * External Genital Lesions: Efficacy $90.6\%$     * Condyloma (Anal Warts): Efficacy $89.3\%$     * PIN 1/2/3 (Penile Intraepithelial Neoplasia): Efficacy $100\%$     * AIN 1/2/3 (Anal Intraepithelial Neoplasia): Efficacy $77.5\%$     * AIN 2/3: Efficacy $74.9\%$     * AIN 1: Efficacy $73\%$     * Condyloma Acuminatum (Anogenital warts caused by HPV): Efficacy $100\%$     * Non-accuminate (Anogenital warts not caused by HPV): Efficacy $60.4\%$

MPox Virus Management

• Primary Treatment:     * Supportive care and pain management for lesions.

• Specific Pharmacotherapy:     * Tecovirimat (TPOXX): Available under an expanded access Investigational New Drug (IND) protocol.     * Indications for TPOXX:         * Severely immunocompromised patients.         * Patients with active skin conditions presenting higher risk for disseminated infection.         * Pregnant or lactating persons, regardless of severity.         * Patients $<18$ years of age, regardless of severity.         * Protracted or life-threatening manifestations, including ocular disease.     * Alternative antiviral options: Cidofovir and Brincofovir (if above criteria are not met).

• MPox Prevention (JYNNEOS):     * Type: $2$-dose subcutaneous vaccine.     * Interval: Second dose given $4$ weeks after the first.     * Target Population (Gay, bisexual, or other MSM) with risk factors in the past 6 months:         1. New diagnosis of at least one STI.         2. More than one sex partner.         3. Sex at a commercial sex venue.         4. Sex at a large public event in a high-transmission geographic area.     * Also recommended for sexual partners of the above individuals or those anticipating these situations.

Summary of Recommendations

• Varivax: $2$-dose series ($12-15$ months; $4-6$ years).

• Shingrix: Routine for immunocompetent adults $\ge 50$ and immunocompromised patients $\ge 18$.

• HPV: Routine for adults up to age $26$ (best at $11-12$ years old). Shared decision for ages $27-45$.

• MPox: Treatment via Tecovirimat (IND); Prevention via JYNNEOS vaccine series for high-risk individuals.