HPV Vaccine Recommendations Including Guidance for Ages 27 to 45

SUMMARY:

The most recent evidence-based HPV vaccine recommendations address when to administer the vaccine and dosing.  One area that has elicited more recent guidance focuses on whether to offer the HPV vaccine to individuals over the age of 26.

• The FDA (October 2018) extended approval of HPV vaccine to individuals age 27 to 45 years
• ACIP (June 2019) voted to
  • Expand routine and catch-up HPV vaccination in males through 26 years of age who are inadequately vaccinated
  • Offer HPV vaccine to individuals age 27 to 45 years who have not been adequately vaccinated based on shared clinical decision making
• ACIP published their final recommendations (August 2019) in the CDC’s Morbidity and Mortality Weekly Report

Children and adults aged 9 through 26 years: HPV vaccination is routinely recommended at age 11 or 12 years; vaccination can be given starting at age 9 years. Catch-up HPV vaccination is recommended for all persons through age 26 years who are not adequately vaccinated.

Adults aged >26 years: Catch-up HPV vaccination is not recommended for all adults aged >26 years. Instead, shared clinical decision-making regarding HPV vaccination is recommended for some adults aged 27 through 45 years who are not adequately vaccinated. HPV vaccines are not licensed for use in adults aged >45 years.

These recommendations for children and adults aged 9 through 26 years and for adults aged >26 years apply to all persons, regardless of behavioral or medical risk factors for HPV infection or disease.

For persons who are pregnant, HPV vaccination should be delayed until after pregnancy; however, pregnancy testing is not needed before vaccination.

Persons who are breastfeeding or lactating can receive HPV vaccine. Recommendations regarding HPV vaccination during pregnancy or lactation have not changed.

• ACIP suggests considering the following points for shared-decision making with adults who are 27 to 45 years of age
  • HPV is very common, usually transient and asymptomatic
  • Although typically acquired in young adulthood, some adults are at risk for acquiring new HPV infection
  • A new sex partner is a risk factor, while those in long-term, mutually monogamous partnerships are not likely to acquire a new HPV infection
  • HPV types: Sexually active adults will likely have been exposed to some HPV types, but not all HPV types are vaccine targets
  • There is no antibody test to determine immunity
  • HPV vaccine has high efficacy in young persons not yet exposed to vaccine-type HPV
  • Lower vaccine effectiveness may be expected in those with HPV risk factors
    • Multiple lifetime sex partners | Previous infection with vaccine-type HPV | immunocompromising conditions
  • HPV vaccines are prophylactic only and can’t prevent infection progression, improve time to clearance or treat HPV-related disease
• In summary, the CDC states

For adults aged 27 years and older, clinicians can consider discussing HPV vaccination with people who are most likely to benefit. HPV vaccination does not need to be discussed with most adults over age 26 years

CDC Dosing Schedule 

• <15 years: 2 doses spaced 6 to 12 months apart
• ≥15 years: 3-dose schedule
  • Initial dose
  • Second dose at 1 to 2 months after initial 
  • Third dose at 6 months after initial 

Updated ACOG HPV vaccine recommendations 

• Routine HPV vaccination is recommended for females and males 
• Target age is 11 to 12 years but can be given through age 26
  • Can be given from age of 9 
• Do not test for HPV DNA prior to vaccination
  • Vaccinate even if patient was tested and is HPV DNA positive
•  If not vaccinated between 11 to 12 years
  • Vaccinate between 13 to 26 years (catch up period)
• Women 27 to 45 years and not previously unvaccinated
  • Use shared clinical decision making
• ACOG “does not recommend that an individual who received the quadrivalent HPV vaccine be revaccinated with 9-valent HPV vaccine, including those aged 27–45 years who previously completed some, but not all, of the vaccine series when they were younger”
• Pregnancy
  • HPV vaccine is not recommended during pregnancy
  • Pregnancy testing prior to HPV vaccination not recommended
  • If vaccination schedule is interrupted by pregnancy, resume postpartum with the next dose
  • HPV vaccine can and should be given to breastfeeding women ≤26 who have not been vaccinated
• Counsel to expect mild local discomfort and that this is not a cause for concern
  • Watch adolescents for at least 15 minutes following vaccination due to risk of fainting in this population

AAP  

• The AAP  has also endorsed the CDC HPV recommendations
  • The HPV vaccine should be normalized as a standard of care
  • Recommendation should be clear and unambiguous 
  • AAP provides multiple strategies (see ‘Learn More – Primary Sources’ below) to engaging with patients including focusing on cancer prevention benefits for all children 

ACS

• The ACS endorses ACIP CDC guidance regarding HPV guidance except for the approach to take with individuals who are 27 to 45 years and not adequately vaccinated

The ACS does not endorse the 2019 Advisory Committee on Immunization Practices recommendation for shared clinical decision making for some adults aged 27 through 45 years who are not adequately vaccinated because of the low effectiveness and low cancer prevention potential of vaccination in this age group, the burden of decision making on patients and clinicians, and the lack of sufficient guidance on the selection of individuals who might benefit

Adjuvant HPV Vaccine to Prevent CIN Recurrence 

• ACOG recommends considering adjuvant HPV vaccine for unvaccinated individuals 27 to 45 years who are undergoing treatment for CIN 2+

Learn More – Primary Sources:

FDA approves expanded use of Gardasil 9 to include individuals 27 through 45 years old

Human Papillomavirus Vaccination for Adults: Updated Recommendations of the Advisory Committee on Immunization Practices (MMWR)

CDC: HPV Vaccination Schedules & Recommendations

ACOG Committee Opinion 809: Human Papillomavirus Vaccination

ACOG Practice Advisory: Adjuvant Human Papillomavirus Vaccination for Patients Undergoing Treatment for Cervical Intraepithelial Neoplasia 2+

AAP: How Pediatricians Can Recommend HPV Vaccination to Parents and Caregivers

CDC Frequently Asked Questions about HPV Vaccine Safety

CDC: HPV Educational Materials For Clinicians

ACS: Human papillomavirus vaccination 2020 guideline update

When LMP and Ultrasound Dates Don’t Match: When to Redate?

CLINICAL ACTIONS:

Historically, dating pregnancies and calculating due dates were left to weekly pregnancy calendars.  However, ultrasound dating, in particular first trimester sonography, has greatly improved our ability to calculate the estimated due date (EDD).  There will be times that dating based on LMP does not match the ultrasound date.

ACOG recommends redating as follows:

• First trimester: based on CRL measurement
  • 8w6d or less: redate if discrepancy is > 5d
  • 9w0d – 13w6d: redate if discrepancy is > 7d

• Second trimester: based on BPD, HC, AC and FL
  • 14w0d – 15w6d: redate if discrepancy is > 7d
  • 16w0d – 21w6d: redate if discrepancy is > 10d
  • 22w0d – 27w6d: redate if discrepancy is > 14d

• Third trimester: based on BPD, HC, AC and FL
  • 28w0d and beyond: redate if discrepancy is > 21d
    • Use caution when redating in the 3rd trimester as discrepancy may reflect growth restriction
    • Management should not be based on ultrasound alone but rather comprehensive clinical assessment

SYNOPSIS:

Clinical determination of EDD, 280 days after the last menstrual period (LMP) still plays a role but may not always be accurate due to variability in length of an individual woman’s cycle length or timing of ovulation.  Accurate dating is vital to pregnancy management, as certain interventions and management decisions may be based on such information including timing of delivery in the case of pregnancy complications.

KEY POINTS:

• First trimester ultrasound is the most accurate time frame for pregnancy dating and can increase the accuracy of the EDD even if LMP is known
• Consider a pregnancy without a dating ultrasound prior to 22 0/7 weeks ‘suboptimally dated’ (refer to Related ObG Topics below)
• Mean sac diameter is not recommended for dating
• In the setting of assisted reproductive technology (ART), the ART derived gestational age should be used for EDD using the age of the embryo and the transfer date
  • The age of the embryo is subtracted from the number of days between ovulation to delivery (280-14 = 266).  For example, if the embryo is 3 days at transfer, the due date is 263 days from the date of transfer.
• If the CRL is greater than 84 mm, biometric parameters should be used to date the pregnancy
• Once the EDD has been established using the LMP and/or first accurate ultrasound measurement, it should be recorded in the medical record and discussed with the patient

Learn More – Primary Sources:

ACOG/AIUM/SMFM Committee Opinion 700: Methods for Estimating Due Date

AIUM Practice Parameter for the Performance of Limited Obstetric Ultrasound Examinations by Advanced Clinical Providers

ACOG AIUM Practice Bulletin 175: Ultrasound in Pregnancy

CDC Guidance on TB Screening for US Healthcare Personnel

SUMMARY:

The CDC performed a systematic review of TB screening, specifically for healthcare personnel and have reassessed the need for serial TB testing.

Updated Recommendations Include

TB screening with an individual risk assessment and symptom evaluation at baseline (preplacement)

TB testing with an interferon-gamma release assay (IGRA) or a tuberculin skin test (TST) for persons without documented prior TB disease or latent TB infection (LTBI)

No routine serial TB testing at any interval after baseline in the absence of a known exposure or ongoing transmission

Encouragement of treatment for all health care personnel with untreated LTBI, unless treatment is contraindicated

Annual symptom screening for health care personnel with untreated LTBI

Annual TB education of all health care personnel

Postexposure Screening and Testing (adequate personnel protection was not used)

SYNOPSIS:

The updated CDC recommendations are based on a comprehensive systematic review of the literature. TB screening includes TB risk assessment, symptom evaluation and TB testing for M. tuberculosis infection.  The CDC also recommends workup for positive TB results or symptoms compatible with TB disease.

KEY POINTS:

• Recent data suggest that unlike in previous eras, US health care personnel may not be at increased risk for LTBI and TB disease from occupational exposures
  • TB rates: 2017 rate has decreased by 73% from 1991 rate and by 42% from 2005
  • CDC Surveillance data (1995-2007): TB incidence rates among health care personnel were similar to those in the general population
  • Recent retrospective cohort study (n=40,000) at a tertiary U.S. medical center in a low TB-incidence state found an extremely low rate of TST conversion (0.3%) with most not attributable to occupational exposure
  • Evidence exists that IGRAs and TSTs have limitations when it comes to serial testing of health care personnel at low risk for LTBI and TB disease
• Baseline (preplacement) screening and testing is required to
  • Provide a basis for comparison in the event of a potential or known exposure to M. tuberculosis
• For healthcare personnel with a positive test and who are asymptomatic
  • If risk assessment is ‘low risk’, follow up with second test (IGRA or TST)
  • Health care personnel should be considered infected only if both the first and second tests are positive

Learn More – Primary Sources:

Tuberculosis Screening, Testing, and Treatment of U.S. Health Care Personnel: Recommendations from the National Tuberculosis Controllers Association and CDC, 2019

Opportunistic Salpingectomy: A Surgical Approach to Reducing Ovarian Cancer Risk

SUMMARY:

ACOG addresses the role of opportunistic salpingectomy in reducing ovarian cancer risk for women undergoing hysterectomy (benign conditions) or cesarean section.  The recommendations apply to women at average ‘population’ risk for ovarian cancer and not those at high risk (for example BRCA mutation carriers). Risks and benefits should be discussed with women considering opportunistic salpingectomy.

Science Behind the Guidance

• “Strong” data suggests that ovarian cancers (including serous, endometrioid, and clear cell) derive from endometrium or fallopian tube and not ovary itself
• Therefore, bilateral salpingectomy at time of hysterectomy or cesarean, even if ovaries are left in situ, should reduce ovarian cancer risk
• Note: Even if the above is correct, some ovarian cancers will arise from the ovary, not the tube | Opportunistic salpingectomy should not be considered 100% preventative

Risks Associated with Opportunistic Salpingectomy

• The following complications have not been demonstrated in women undergoing opportunistic salpingectomy
  • Infection | transfusion | readmission | postop complications
  • Ovarian function does not appear to be impaired
  • See ‘Related ObG Topics’ below for research summaries
• ACOG states that “salpingectomy at the time of hysterectomy or as a means of tubal sterilization appears to be safe”

Benefits Compared to Bilateral Salpingo-Oophorectomy (BSO)

• Literature supports the option of opportunistic salpingectomy for ovarian cancer risk reduction in the setting of benign surgery
• BSO and resultant surgical menopause elevates risk for the following
  • Cardiovascular disease
  • Osteoporosis
  • Cognitive impairment
  • All cause-mortality
  • Cancers (lung, colon, bladder and ‘any cancer’ – see BMJ study below in ‘Learn More – Primary Sources’)
• There is “little benefit” to ovarian conservation >65 years of age

KEY POINTS:

Technique

• Ideally, tube should be removed from fimbriated end to uterotubal junction
  • If not possible, remove as much as safely feasible
• Remove or cauterize fimbrial tissue if adherent to the ovary
• Choice of opportunistic salpingectomy should not impact route of hysterectomy

Learn More – Primary Sources:

BMJ (2017): Removal of all ovarian tissue versus conserving ovarian tissue at time of hysterectomy in premenopausal patients with benign disease: study using routine data and data linkage

Tips and Tricks for Performing Salpingectomy at the Time of Laparoscopic Hysterectomy

ACOG Committee Opinion 774: Opportunistic Salpingectomy as a Strategy for Epithelial Ovarian Cancer Prevention

Chronic Hypertension in Pregnancy: Evaluation and Management

CLINICAL ACTIONS:

ACOG has released recommendations on chronic hypertension in pregnancy. Management of chronic hypertension in pregnancy depends on gestational age and symptoms. Initial assessment, including identification of end-organ damage and evaluation of medications will drive treatment and delivery planning.

• Evaluation
• Medical Management
• Fetal Surveillance
• Timing of Delivery
• Postpartum

Evaluation

• Ideally preconception or the first prenatal visit is the optimal time to establish a diagnosis (primary vs. secondary hypertension) and assess for end-organ damage, based on a thorough history and physical

Laboratory tests

• Complete blood count
• Liver function tests
• Serum electrolytes (esp. potassium)
• Renal Function Tests
  • Serum creatinine
    • Mild renal impairment: Cr 0.9-1.4
    • Moderate renal impairment: Cr 1.4-2.4
    • Severe renal impairment: Cr 2.4-2.8
  • Blood urea nitrogen
  • Spot urine protein/creatinine to screen for proteinuria
    • <0.15 denotes patient spilling <300 mg for a 24-hour sample
    • If spot urine ratio elevated, do 24-hour urine
    • Note: 24-hour urine assessment not required if normal Cr and spot urine ratio <0.15
  • Order ECG if ≥1 of the following
    • Chronic hypertension present >4 years
    • Maternal age >30 years with long standing hypertension
    • History abnormal ECG
    • Additional risk factors (i.e. long-standing diabetes)

SYNOPSIS:

The benefits of treating mild to moderate chronic hypertension in pregnancy are not clear, thus a conversation with patients (i.e. shared decision-making) is warranted. Timing of delivery depends on severity of disease and gestational age. Women with chronic hypertension remain at risk for complications during the postpartum period so early follow-up is recommended.

KEY POINTS:

Medical Management

Choice of Antihypertensive

• Most commonly used antihypertensives
  • Labetalol – ‘preferred’: 200 to 2,400 mg/d po (2 to 3 divided doses)
    • Initiate at 100 to 200 mg twice a day
    • Watch for potential bronchospasm
    • Avoid in women with asthma, heart disease, congestive heart failure, bradycardia and heart block
  • Nifedipine – ‘preferred’: 30 to 120 mg/d po (avoid sublingual)
    • Initiate at 30 to 60 mg daily (extended release)
    • Avoid in women with tachycardia
  • Methyldopa – ‘less favored’: 500 to 3,000 mg/d po (2 to 4 divided doses)
    • Initiate at 250 mg twice or 3 times/day
    • May not be as effective and limited by side-effects such as dizziness, depression or sedation
  • Second line therapy
    • HCTZ (considered a safe diuretic)
  • Other medications are available and may be used with MFM consultation
  • Note: The following medications are not recommended
    • Ace inhibitors | Angiotensin II receptor blockers | Renin inhibitors | Mineralocorticoid receptor antagonists | Atenolol (due to risk for FGR and LBW)

Threshold for Initiation of therapy  

• Based on the CHAP Trial (see ‘Related ObG Entries’ below), ACOG and SMFM have revised guidance regarding initiation of therapy for women with mild chronic hypertension during pregnancy 
• Start antihypertensive therapy at >140/90 

Patient on medications prior to pregnancy

• In the absence of mitigating factors or side effects
  • Maintain on their medications
  • Do not discontinue and wait until blood pressures in the severe range to initiate therapy
  • Individualize decision whether to discontinue
• Replace contraindicated medications and monitor therapy and BP targets accordingly

Target BP

• ACOG
  • Notes that RCT (CHAP Trial) demonstrated benefit of using 140/90 as threshold but did not determine ideal target BP or if there is a BP at which growth restriction may be a concern
• SMFM
  • “…recommends treatment with antihypertensive therapy for mild chronic hypertension in pregnancy to a goal BP <140/90 mm Hg”

Aspirin

• Use aspirin for risk reduction (see ‘Related ObG Topics below)
  • Initiate daily low dose aspirin (81 mg) between 12 to 28 weeks gestation

Fetal Surveillance

• Antepartum
  • Timing/interval of testing not well established
  • Assess fetal growth in the 3^rd trimester
• Intrapartum
  • Continuous fetal monitoring

Timing of Delivery

• Chronic HTN and no medications
  • Delivery <38w0d not recommended
• Chronic HTN well controlled on maintenance antihypertensive medication
  • Delivery <37w0d not recommended
• Chronic HTN with superimposed preeclampsia without severe features
  • Expectant management with delivery at 37w0d
• Chronic HTN with superimposed preeclampsia with severe features
  • Expectant management under certain circumstances until delivery at 34w0d (inpatient care only)
  • Initiation of antenatal steroids as per guidelines (see ‘Related ObG Topics below)
• Note: When considering the latest time to deliver, ACOG states

…expectant management beyond 39 0/7 weeks of gestation should only be done after careful consideration of the risks and benefits and with appropriate surveillance

Postpartum

• Early ambulatory visits (within 2 weeks) postpartum
  • Severe HTN or superimposed preeclampsia may develop for the first time in the postpartum period
• Patient may return to prepregnancy regimen and managed appropriately, without fetal considerations
  • Note: Avoid methyldopa in postpartum period due to risk for depression
• Careful medication titration to achieve BP no higher than 150/100 mm Hg
• Analgesia
  • NSAIDs were not associated with BP elevation based on data from women with preeclampsia with severe features
• Breastfeeding
  • Antihypertensives can be used in breastfeeding women
  • Propranolol and labetalol are preferred due to lower levels in breast milk compared to some other medications
  • ACE inhibitors can also be used safely unless high doses required
  • Calcium channel blockers are not associated with adverse outcomes
  • Note: Diuretics may reduce quantity of breast milk

Learn More – Primary Sources:

ACOG Practice Bulletin 203: Chronic Hypertension in Pregnancy

ACOG: Clinical Guidance for the Integration of the Findings of the Chronic Hypertension and Pregnancy (CHAP) Study

SMFM Statement: Antihypertensive therapy for mild chronic hypertension in pregnancy (The CHAP Trial)

Shingles Vaccine: CDC/ACIP Recommendations 

SUMMARY:  

In October 2017, the FDA approved and ACIP recommended a Shingrix (RZV) vaccine for adults ≥50 years of age. Zostavax (ZVL) is no longer available for use in the United States, as of November 18, 2020.

• Herpes Zoster and Postherpetic Neuralgia
• Zoster Vaccine Recommendations
• Clinical Guidance
• Counseling and Adverse Events
• Special Populations

Herpes Zoster and Postherpetic Neuralgia 

• Herpes zoster is a localized, painful, cutaneous eruption resulting from reactivation of latent varicella zoster virus (VZV) 
• Approximately one million cases occur each year in the United States  
• Incidence increases with age 
  • 50 to 59 years of age: 5 cases per 1,000  
  • ≥80 years: 11 cases per 1,000  
• Postherpetic Neuralgia is the most common complication  
  • Defined as persistent pain for at least 90 days following the resolution of the herpes zoster rash 
  • Occurs in 10 to 13% of herpes zoster cases in persons aged >50 years and risk increases with age 

Herpes Zoster Vaccine Recommendations  

Shingrix is recommended for the prevention of herpes zoster and related complications for immunocompetent adults aged ≥50 years 

• Two doses of Shingrix provides strong protection against shingles and postherpetic neuralgia (PHN), the most common complication of shingles
  • Shingles Prevention: In adults 50 to 69 years old who got two doses, Shingrix was 97% effective; among adults 70 years and older, Shingrix was 91% effective
  • Postherpetic Neuralgia: In adults 50 to 69 years old who got two doses, Shingrix was 91% effective; among adults 70 years and older, Shingrix was 89% effective
• Shingrix protection remained high (more than 85%) in people 70 years and older throughout the four years following vaccination
• Shingrix is recommended for the prevention of herpes zoster and related complications for immunocompetent adults who previously received Zostavax or have already had herpes zoster
• There is no maximum age for Shingrix

Clinical Guidance 

• Administer 2 doses (0.5 mL each) administered intramuscularly 2 to 6 months apart 
• Shingrix may be used in adults aged ≥50 years, irrespective of prior receipt of varicella vaccine or Zostavax 
• If patient previously received Zostavax
  • Consider the patient’s age and when he or she received Zostavax to determine when to vaccinate with Shingrix | Differences in efficacy between Shingrix and Zostavax are most pronounced among older patients
  • Studies examined the safety of Shingrix vaccination five or more years after Zostavax vaccination | Shorter intervals were not studied, but there are no theoretical or data concerns to indicate that Shingrix would be less safe or effective if administered less than five years after a patient received Zostavax
• Screening for a history of chickenpox (varicella) not required  
  • Recombinant and adjuvanted vaccines, such as Shingrix, can be administered concomitantly at the same visit, at different anatomic sites, with other adult vaccines (e.g., influenza and pneumococcal vaccines) 
• Shingrix is not a treatment for herpes zoster or postherpetic neuralgia  
• Pregnancy and breastfeeding 
  • There are no available data to establish whether Shingrix is safe in pregnant or lactating women   
  • Consider delaying vaccination with Shingrix in such circumstance 

KEY POINTS:  

Counseling and Adverse Events  

• Reactions to the first dose of Shingrix did not strongly predict reactions to the second dose 
• Vaccine recipients should be encouraged to complete the series even if they experienced a grade 1 to 3 reaction to the first dose of Shingrix  
  • In studies, Grade 3 solicited symptoms were defined as “preventing normal everyday activity” (pain, headache, fatigue, gastrointestinal symptoms, myalgia, shivering) | surface diameter >100 mm (redness/swelling) | tympanic/oral/axillary temperature >39.0 °C (fever)  
  • Grade 3 unsolicited adverse events were also defined as “preventing normal, everyday activities” 

Adverse Events

• The impact of prophylactic analgesics in conjunction with Shingrix has not been studied 
• Adverse local events are relatively common and include 
  • Pain  
  • Redness  
  • Swelling  
• General adverse reactions include  
  • Myalgia  
  • Fatigue  
  • Headache  
  • Shivering  
  • Fever  
  • Gastrointestinal symptoms
• Severe (rare) events include
  •  Difficulty breathing
  • Wheezing
  • Hives
  • Pale skin
  • Fast heartbeat
  • Dizziness 
• Contraindications 
  • History of severe allergic reaction (e.g., anaphylaxis) to any component of the vaccine OR after previous dose  
  • Acute episode of herpes zoster | Wait until acute episode has abated 

Special Populations 

• Persons with a history of herpes zoster 
  • Adults with a history of herpes zoster should receive Shingrix as herpes zoster can recur  
• Persons with chronic medical conditions (e.g., chronic renal failure, diabetes mellitus, rheumatoid arthritis, and chronic pulmonary disease) 
  • Shingrix should be used 
• Immunocompromised persons  
  • Shingrix may be used in persons taking low-dose immunosuppressive therapy (e.g., <20 mg/day of prednisone or equivalent or using inhaled or topical steroids), persons anticipating immunosuppression or who have recovered from an immunocompromising illness
  • Advisory Committee on Immunization Practices recommended 2 RZV doses for prevention of herpes zoster and related complications in immunodeficient or immunosuppressed adults aged ≥19 years
  • Second RZV dose should be given 2 to 6 months after the first | For persons who are or will be immunodeficient or immunosuppressed and who would benefit from a shorter vaccination schedule, the second dose can be administered 1 to 2 months after the first
• Persons known to be VZV negative 
  • Screening for a history of varicella (either verbally or via laboratory serology) is not recommended 
  • However, in persons known to be VZV negative via serologic testing, ACIP guidelines for varicella vaccination should be followed 
    • All healthy adults should be assessed for varicella immunity, and those who do not have evidence of immunity should receive 2 doses of single-antigen varicella vaccine 4-8 weeks apart 
    • Shingrix has not been evaluated in persons who are VZV seronegative and the vaccine is not indicated for the prevention of chickenpox (varicella) 

Learn More – Primary Sources:

CDC MMWR: Recommendations of the Advisory Committee on Immunization Practices for Use of Herpes Zoster Vaccines

Use of Recombinant Zoster Vaccine in Immunocompromised Adults Aged ≥19 Years: Recommendations of the Advisory Committee on Immunization Practices — United States, 2022 | MMWR (cdc.gov)

CDC: Shingles (Herpes Zoster) Vaccination Information for Healthcare Providers

FDA: SHINGRIX (Zoster Vaccine Recombinant, Adjuvanted)  

CDC Epidemiology and Prevention of Vaccine-Preventable Diseases; The Pink Book: Course Textbook – 13th Edition (2015)

Immunogenicity, reactogenicity and safety of 2 doses of an adjuvanted herpes zoster subunit vaccine administered 2, 6 or 12 months apart in older adults: Results of a phase III, randomized, open-label, multicenter study 

Lyme Disease: Diagnosis and Treatment

SUMMARY:

Lyme disease is a serious condition caused by six species of spirochetal bacteria, most commonly Borrelia burgdorferi in North America, following a deer tick bite that requires treatment. Clinical disease can occur within days to several months following a tick bite. Lyme disease is endemic to the northeastern states from Virginia to eastern Canada, the upper Midwest, particularly Wisconsin and 
Minnesota, and northern California. The following provides key points regarding diagnosis, treatment, prophylaxis and tick removal.

DIAGNOSING LYME DISEASE:

Early localized disease features:

• Erythema migrans (EM)
  • 70 to 80% of infected individuals
  • At site of tick bite approximately day 7 to 14 days after bite (range 3 to 30 days) 
  • Expands slowly and develops central clearing  
  • May have multiple lesions indicating disseminated disease (not multiple tick bites) 
• Fever, headache, and fatigue
• Joint and muscle aches
• Swollen lymph nodes

Ixodes tick and Erythema Migrans images courtesy DermNetNZ.org 

Early disseminated disease features:  

• Neurologic symptoms: lymphocytic meningitis | cranial nerve palsies |radiculopathy | mononeuropathy multiplex | peripheral neuropathy 
• Carditis : palpitations, chest pain, light headedness, fainting, shortness of breath, and difficulty breathing with exertion 
• Multiple EM lesions  
• Conjunctivitis 

Late disease features (months to years after tick bite):

• Large joing polyarthralgia
• Confluent mononeuropathy multiplex
• Encephalomyelitis

Testing

Note: The CDC has updated the Lyme laboratory screening algorithm

• CDC still recommends the two step approach
  • Step 1: Serologic testing using a sensitive enzyme immunoassay (EIA) or immunofluorescence assay
  • Step 2: Follow step one with a western immunoblot assay for specimens yielding positive or equivocal results
• Modified two-step approach
  • Two enzyme immunoassays (EIA) are run concurrently or sequentially
  • The CDC states that

When cleared by FDA for this purpose, serologic assays that utilize a second EIA in place of western immunoblot assay are acceptable alternatives for the serologic diagnosis of Lyme disease

Note: When EM is present and patient has been to a Lyme endemic area serologic testing is not recommended and treatment can be initiated following clinical diagnosis  

KEY POINTS:

• Two-tiered serologic testing is more sensitive the longer infection has been present
• Myth that Lyme disease can become chronic and no longer detectable on lab testing
• Testing can remain positive for years so can not be used to test for cure 

Treatment

• First line therapy for adults with early localized Lyme disease
  • Doxycycline: 100 mg twice per day for 10 days, or
  • Amoxicillin: 500 mg 3 times per day for 14 days, or
  • Cefuroxime axetil (500 mg twice per day) for 14 days
• Therapy for early disseminated Lyme disease with neurologic manifestations: 
  • Doxycycline  100 mg twice per day for 14 to 21 days, or
  • Ceftriaxone IV 2 g daily for 14 to 21 days  
• Therapy for early disseminated Lyme disease with mild carditis (1st degree AV block with PR interval ≤ 300 milliseconds:
  • Doxycyline 100 mg twice per day for 14 to 21 days, or 
  • Amoxicillin 500 mg three times per day for 14 to 21 days, or 
  • Cefuroxime 500 mg twice per day orally for 14 to 21 days 
• Therapy for early disseminated Lyme disease with severe carditis (symptomatic, 1st degree AV block with PR interval ≥ 300 milliseconds 
  • If severe carditis (symptomatic, 1st degree AV block with PR interval ≥300 milliseconds, 2nd or 3rd degree AV block) then patient should be admitted for telemetry monitoring and treated with Ceftriaxone IV 2 g daily for 14 to 21 days 
• For treatment of late Lyme disease, including arthritis, the antibiotic course is extended to 28 days using the above antibiotics for early localized disease 
• The CDC concurs with the following IDSA recommendation that advises strongly against the treatment of chronic Lyme disease (highest level of evidence ‘I’, based on randomized controlled trials) as overtreatment with unnecessary antibiotics may prove fatal (e.g. septic shock, C. difficile, paraspinal abscess and osteomyelitis): 

There is no convincing biologic evidence for the existence of symptomatic chronic B. burgdorferi infection among patients after receipt of recommended treatment regimens for Lyme disease. Antibiotic therapy has not proven to be useful and is not recommended for patients with chronic (⩾6 months) subjective symptoms after recommended treatment regimens for Lyme disease.

Prophylaxis: Management of asymptomatic individuals following a tick bite

• Routine use of antimicrobial prophylaxis or serologic testing is not recommended
• A single dose of doxycycline may be offered to adult patients (200 mg dose) when all the following are met:
  •  The attached tick can be reliably identified as an adult or nymphal I. scapularis deer tick that is estimated to have been attached for ⩾36 h based on the degree of engorgement of the tick with blood or on certainty about the time of exposure to the tick
  • Prophylaxis can be started within 72 h of the time that the tick was removed
  • Ecologic information indicates that the local rate of infection of these ticks with B. burgdorferi is ⩾20% (occurs in parts of New England, in parts of the mid-Atlantic States, and in parts of Minnesota and Wisconsin)
  • Doxycycline is not contraindicated

Tick Removal

• The risk of getting a tick-borne disease is small if the tick is removed soon after it becomes attached
  • Deer ticks must remain attached one to two days to transmit Lyme disease, and about one day for other tick-borne diseases
• Use tweezers to grasp the tick close to its mouth
• Gently and slowly pull the tick straight outward
• To avoid contact with the bacteria, if present, do not squeeze the ticks’ body
• Wash the area and apply an antiseptic to the bite
• Watch for early signs and symptoms of Lyme disease

Learn More – Primary Sources:

CDC MMWR: Serious Bacterial Infections Acquired During Treatment of Patients Given a Diagnosis of Chronic Lyme Disease — United States 

CDC: Lyme Disease Diagnosis, Treatment and Testing

Clinical Practice Guidelines by the Infectious Diseases Society of America (IDSA), American Academy of Neurology (AAN), and American College of Rheumatology (ACR): 2020 Guidelines for the Prevention, Diagnosis and Treatment of Lyme Disease

Signs and Symptoms of Untreated Lyme Disease

Minnesota Department of Natural Resources: Deer Ticks

CDC: Lyme Disease Transmission

JAMA: Lyme Disease in 2018 – What Is New (and What Is Not)

FDA clears new indications for existing Lyme disease tests that may help streamline diagnoses

CDC: Updated CDC Recommendation for Serologic Diagnosis of Lyme Disease

BMJ State-of-the-Art Review: Lyme borreliosis: diagnosis and management 

ACOG Guidance: Emergency Treatment for Severe Hypertension in Pregnancy

Summary:

Severe hypertension can be a life-threatening event during pregnancy and requires special vigilance in the postpartum period, particularly following hospital discharge. The goal of treatment is to control hypertension and prevent seizures.  Uncontrolled hypertension can lead to heart failure, myocardial ischemia, renal injury and stroke.

When to Treat:

Urgently treat acute onset severe hypertension in pregnancy or postpartum period

• SBP ≥160 and and/or DBP ≥110 mm Hg persisting for 15 minutes
  • systolic BP a predictor of maternal morbidity/mortality

First Line Therapy:

Nifedipine

Hydralazine

Labetalol

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Immediate Release Oral Nifedipine

Onset

• 5 to 10 minutes

Administration

• 10 to 20 mg orally
• Repeat in 20 minutes if needed
• Then 10 to 20 mg every 2 to 6 hours
• Maximum dose: 180 mg

Medication Risks

• Maternal tachycardia and headaches

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IV Hydralazine

Onset

• 10 to 20 minutes

Administration

• IV
  • 5  to 10 mg IV (or IM)
  • Then 5 to 10 mg IV every 20 to 40 minutes
• Infusion
  • 0.5 to 10 mg/hr
• Maximum dose: 20 mg

Medication Risks 

• Maternal hypotension and headaches
• Abnormal FH tracings

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IV Labetalol

Onset

• 1 to 2 minutes

Administration 

• IV
  • 10 to 20 mg IV
  • Then 20 to 80 mg every 10 to 30 minutes
• Infusion
  • 1 to 2 mg/min
• Maximum dose: 300 mg

Medication Risks 

• Avoid in the following clinical settings
  • Asthma
  • Preexisting myocardial disease | Decompensated cardiac function | Heart block | Bradycardia

Note: ACOG states that “any of these agents can be used to treat acute severe hypertension in pregnancy” | An approach detailed in ACOG guidance uses “an initial regimen of labetalol at 200 mg orally every 12 hours and increase the dose up to 800 mg orally every 8–12 hours as needed (maximum total 2,400 mg/d). If the maximum dose is inadequate to achieve the desired blood pressure goal, or the dosage is limited by adverse effect, then short-acting oral nifedipine can be added gradually”

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Seizure Prophylaxis: Magnesium Sulfate

• Remains drug of choice for seizure prophylaxis
• Magnesium sulfate should not be used to reduce blood pressure
• See more on magnesium sulfate in ‘Related ObG Topics’

When to Use

• Severe features of preeclampsia
  • Administer to all women
• No severe features of preeclampsia and systolic BP > 140 and < 160 mm Hg or diastolic BP > 90 and < 110 mm Hg
  • There is no consensus on this matter as prophylaxis will reduce eclampsia but 1 in 100 to 129 women need to be treated and side effects (although not life threatening) will increase
  • ACOG states that the decision to use magnesium sulfate when severe features are not present should be the decision of the “physician or institution, considering patient values or preferences, and the unique risk-benefit trade-off of each strategy”

Delivery and Postpartum

• Vaginal delivery
  • Continue infusion 24 hours postpartum
• Cesarean
  • Begin infusion (if not yet running) before surgery and continue 24 hours postpartum
  • Discontinuing prior to operative vaginal birth or cesarean section to avoid uterine atony or anesthetic drug interactions is not recommended

Administration

• Loading dose of 4 to 6 g administered per infusion pump over 20 to 30 minutes (i.e., slowly) followed by a maintenance dose of 1 to 2 g per hour as a continuous intravenous infusion
• IM option if IV access limited
  • 10 g initially as a loading dose (5 g IM in each buttock) followed by 5 g every 4 hours
  • Mix with 1 mL xylocaine 2% to alleviate pain

Learn More – Primary Sources:

ACOG Practice Bulletin 222: Gestational Hypertension and Preeclampsia

ACOG II Severe Hypertension in Pregnancy Bundle

FIGO: A literature review and best practice advice for second and third trimester risk stratification, monitoring, and management of pre-eclampsia