sign in sign up
<<
Home , Cholera vaccine, Japanese encephalitis, Measles vaccine, Meningococcal vaccine, Polio vaccine, Rabies vaccine

Travel Don’t Leave Home without Them

Maria Lanzi, MS, MPH, ANP‐BC, COHN‐S, CTH Adult Nurse Practitioner/Program Coordinator Employee Occupational Health VA Medical Center Conflict of Interest

• The opinions expressed and related educational content are my own and do not necessarily reflect the formal opinions or recommendations of the Veterans Health Administration

• I am solely responsible for the content of this presentation including copyright and other intellectual property compliance

• I serve as a Member of the Advisory Committee on Practices (ACIP) Adult Immunization Working Group Objectives

Review the of common travel related preventable diseases

Review the current ACIP recommendations for US available Vaccines

Understand the importance of travel immunization in supporting goals

Understand how workplace travel medicine and immunization programs can support public health preparedness Reflection

A young man, a cook by trade, is ill one day at work. He thinks nothing of it, “just a bad cold”. But within a few hours, many of his companions have become ill.

His companions travel to Europe for a pre‐planned group trip. Unbeknownst to them, they were all carrying a deadly . International Travel

In 2017 Americans took

2.3 billion person‐trips for either business or leisure1 • ~25% go to developing countries2 • Tropical and infectious diseases • Hazardous Environment (including transportation) • Limited Health Care Resources

1 US Travel Association 2 CDC International Travel: Busiest Locations

In 2017 ~ 76.5 million international arrivals including 38.5 million from overseas Air Cruise 1. New York (JFK) 1. Miami, FL 2. Miami (MIA) 2. Orlando, FL 3. Atlanta (ATL) 3. Fort Lauderdale. FL 4. Newark (EWR) 4. Cozumel, Mexico 5. Los Angeles (LAX) 5. Nassau, Bahamas 6. (ORD) 7. Washington (IAD) 8. San Francisco (SFO) 9. Houston (IAH) 10. Philadelphia (PHL) Larger Vessels, Faster Travel, Longer Distances, Port Populations

• Greater number of people exposed • Greater potential for disease outbreaks Capable of carrying 868 passengers • Confined areas for incubation • particular time and place • small and localized group • impact thousands of people • Can cross an entire continent • occurs across multiple countries • People travel while ill • Spread of disease during incubation period

Capable of carrying 5,479 passengers Global Travel: “It’s a small world after all” Current Outbreaks • – and Nigeria3 • – Papua New Guinea3 • – • –everywhere • 41,000 cases in Europe in first 6th months of 20184 • Including: Ukraine‐23,070; – 2,576; Greece – 2,130; Italy – 2,020; Uk‐760; • South American cases: ‐ 3,500 Brazil – 1,0535 • /South East Asia: 45,000 4 • 124 cases in 21 states in US since January6 • 9 outbreaks

3 CDC Travel Advisory 4 World Health Organization. “Measles cases hit record high in the European Region”. 20 August 2018 5 Pan American Health Organization (PAHO), Epidemiological Update, 20 July 2018 6 CDC. Measles Cases and Outbreaks. Special Populations

• Immunocompromised travelers • Travelers visiting friends and relatives Seeking health services (transplants, dental, cosmetic surgery) Adventure/extreme travel • Elderly travelers • Students • Long‐stay travelers • Relief workers Pre‐Travel Consultation

Individual Risk Assessment • Specific Itinerary • Purpose of Trip • Duration of Trip • Season of Travel • Activities • Cultural Biases • Underlying Health Issues Vaccine Assessment

• Incidence of Vaccine Preventable Disease  Impact of Vaccine Preventable Disease  Risks of Vaccine  Benefits of Vaccine • Vaccine Costs

• At least 8 weeks before leaving • At least 12 weeks if long term trip (>4 weeks) Travel Vaccines: “Don’t Leave Home without Them”

The “Routine” • B, Tetanus/Tdap, , Pneumococcal

The “Usual 3” Recommended • Hepatitis A, Typhoid,

The “Special group” Recommended • Meningococcal, Measles, Polio, , Tick Borne ,

The “Required” to cross International Boarders  • Incurable Carcinogen • 80% of Hepatocellular carcinoma

• In US: • 5,000 HBV related deaths, annually • Chronic HBV ~1.4 million Americans • HBV related health and productivity costs ~ $700 million Hepatitis B Intermediate to High Risk Areas: >2% prevalence

• HepB‐alum: 3‐dose series (usual dose: 10mcg/1mL) • yeast derived recombinant single • Usual schedule: 0,1, and 4‐6 months • Accelerated schedule: 0, 1, and 4 months • Minimal intervals • 4 weeks between dose 1 and 2 • 8 weeks between dose 2 and 3 as long as • 16 weeks between dose 1 and 3 HepB‐CpG: 2 dose series (0.5mL) • yeast derived recombinant single antigen • novel immunostimulatory sequence adjuvant6 Annals Internal Medicine, 21 Nov 2017 • Usual Schedule: 0, 1 month

6 FDA. Product approval information: package insert. Heplisav‐B. Silver Spring, MD: US Department of Health and Human Services, Food and Drug Administration; 2018 : Small synthetic immunostimulatory cytidine‐phosphate‐guanosine oligodeoxynucleotide (CpG‐ODN) motifs (1018 adjuvant). The 1018 adjuvant binds to Toll‐like receptor 9 to stimulate a directed immune response to HBsAg. Hepatitis A • Mild to severe illness • Can cause Fulminant Hepatitis • Mortality for those > 50 years old • may be as high as 1.8%

• Fecal‐oral • lack of safe water /poor sanitation

• ~1.4 million global cases annually

• Epidemics can be explosive and cause significant economic losses

Inactivated Hepatitis A Virus . Series of 2: 0, 6 ‐12 months (1mL) . 82% effective post 1st dose . 94‐100% effective post 2nd dose . Never restart • If leaving < 2 weeks AND >40 years, immunocompromised, chronic disease or other chronic medical condition • Hep A #1 AND Hep A IG (0.1 mL/kg) (separate injection sites) • One dose of HAV IG is effective for ~4 weeks Typhoid (Fever) Salmonella enterica Typhi

• Systemic bacterial illness – Initially non-specific • fecal-oral transmission

• are the only source and reservoir • Long term carrier state occurs

• Globally: ~ 21.5 million cases per year • ~216,500 deaths per year

• US: ~5,700 cases • 75% associated w/travel - South Asia

• Highest risk: VFR (friends, relatives) • especially those traveling to Indian subcontinent

Crump, J. Luby, S., & Mintz, E. (2004). The global burden of . Bulletin of the World Health Organization, 82 (5), 346‐353.

Vi Capsular polysaccharide (ViCPS)  Injectable, one dose  2 years  55-65% effective Oral, 4 dose, LIVE-attenuated (S. typhi strain )  5 years  65-70% effective  Must be completed 1 week before departure  1 hour before meal with cold/tepid water  Avoid alcohol within 1 hour of dosing  Not if on steroids/TNFs Cholera

• Gram negative bacterium Vivrio cholerae • Worldwide: 3-5 million cases each year • 100,000 deaths • 5 -10%: severe “rice watery stools” diarrhea which rapidly leads to dehydration and within 3 days, but death can occur within hours • Vaccine is appropriate for and refugee workers to areas in high risk situations • Several are effective in the treatment of cholera, including , ciprofloxacin, and azithromycin, assuming that the cholera strain is sensitive Cholera

• No is 100% effective • Standard Infection Prevention and Control Measures Cholera Vaccines

Vaxchora –LIVE ORAL • against serogroup O1 for 18‐64 years old • Traveling to areas of active O1 transmission • Single dose –10 days before departure • Needs to be reconstituted and consumed within 15 minutes • No eating/drinking 60 minutes before or after dose • Rapid wane of effectiveness • Multiple side effects

• Not Available in US: ( and Europe) • Dukoral and ShanChol - oral inactivated whole vaccines

• Highest incidence • belt of sub‐Saharan • Epidemic incidence rate • can approach 1000/100,000 or 1% of population

• 6 clinically significant serogroups • Sporadic cases • Outbreaks • Large epidemics Clinically Significant Meningococcal

• Serogroup A: • Leading cause of epidemic meningitis worldwide • Most prevalent serogroup in Africa and • Rare in Europe and the Americas • Serogroup B: • Major cause of endemic disease in Europe and the Americas • Predominant group in infants • Separate vaccine from ACYW • Serogroup C: • major cause of endemic disease in Europe and N. America • Multiple outbreaks in schools/communities • New strain in Africa Clinically Significant Meningococcal

• Serogroup Y: • Infrequent world wide • emerged in US in 1990s • Serogroup W‐135: • Infrequent world wide • global outbreak – 2000 pilgrimage • Serogroup X: • Infrequent worldwide • small outbreaks reported in Africa Meningitis Outbreak : MenACW135Y

Conjugate (attenuated diphtheria toxin) vaccine • Reduces nasal carriage • 10 day before travel • Efficacy lasts about 3 - 5 years • Persons who remain at risk - vaccinate every 5 year • Consider >55 years of age - use is off label

Meningococcal B Vaccines • not recommended for international travel Measles

• Transmission • Droplets • airborne spread • Direct contact • Nasal or throat secretions • Endemic • Africa, Asia, Europe, Oceania • periodic large outbreaks

Travelers who are not immune are at risk Global Measles Outbreak US Measles Outbreak

Year Number of Cases 2010 63 2011 220 2012 55 2013 187 2014 667

2015 180 Public health agency response to a single measles 2016* 86 case range from $5,655 through $181,679

Public Health Economic Burden Associated with Two Single Measles Case Investigations — 2017* 120 Colorado, 2016–2017; MMWR/ November 24, 2017 / 66(46);1272–1275 2018 124

https://www.cdc.gov/measles/cases‐outbreaks.html

Traveling to measles endemic/outbreak areas: MMR born before 1957 considered immune to measles Boost: born during or after 1957 unless • contraindicated* • have documentation of >1 dose • history of measles based on health‐care provider diagnosis • laboratory evidence of were previously vaccinated with killed measles vaccine were vaccinated with an unknown type of measles vaccine during 1963—1967

If Unsure: Titer Poliomyelitis

• Highly Infectious: R0: 5 ‐ 7 • Humans only • Multiplies in the oropharyngeal and intestinal mucosa • Long Infectious period: • Immediately before and up to 2 weeks after symptoms appear • Excreted Feces infected for many weeks • Transmission fecal/oral route • particularly in areas with poor hygiene • Enterovirus: : PV1, PV2 or PV3 Poliomyelitis

Clinical Picture •~ 72% asymptomatic ‐ still infectious •~ 25% ILI mild illness ‐ resolves in 2 –5 days •~ 2‐3% invades • Paresthesia (mainly in legs) • 1 out of 25 ‐ Meningitis • 1 out of 200 – irreversible paralysis • Flaccid Paralysis ‐ matter of hours • 5% to 10% respiratory muscles (mortality) Ongoing Poliovirus Transmission

• Endemic: , , • never stopped transmission of wild type polio

• Infected with wild poliovirus • Afghanistan, Equatorial , , • , Israel, , Nigeria

• Exporting wild poliovirus • , Pakistan and

• Circulating vaccine‐derived poliovirus (cVDPV) a marker of poor oral (OPV) coverage • , Syria, DRC cVDPV Polio Vaccine (IPV) US: exclusively IPV since 2000

• Adults, never been vaccinated ‐ 3 doses of IPV • 2 doses separated by 4‐8 weeks • 3rd dose: 6‐12 months after the 2nd dose • If travel is in less than 8 months • If > 8 weeks available: • 3 doses >= 4 weeks apart • If >4 weeks < 8 weeks: • 2 doses >= 4 weeks apart • If < 4 weeks: single dose IPV Polio Vaccine (IPV) US: exclusively IPV since 2000

Traveling to areas with WPV or VDPV ‐ actively circulating • Prior to May 5, 2014: • Adults, fully vaccinated • Duration of immunity is unknown • One single lifetime booster

Public Health Emergency (WHO) declared in May 2014 • Staying>4 weeks: proof of polio when departing • between 4 weeks and 12 months before the date of departure • Since May 5, 2014: when departing WPV countries • Since November 2014: when departing VDPV countries Temporary polio vaccine recommendations7 Afghanistan, Nigeria, Pakistan, Papua New Guinea, and Somalia • Ensure all residents and long‐term visitors (staying >4 weeks) of all ages receive a dose of inactivated polio vaccine (IPV) or bivalent oral polio vaccine (bOPV) between 4 weeks and 12 months before leaving the country • Ensure that anyone needing to leave the country in less than 4 weeks who has not received a dose of IPV or bOPV in the previous 4 weeks to 12 months get a dose before leaving the country

Democratic , and Syria • Encourage all residents and long‐term visitors (staying >4 weeks) of all ages receive a dose of inactivated polio vaccine (IPV) or bivalent oral polio vaccine (bOPV) between 4 weeks and 12 months before leaving the country. • Encourage that anyone needing to leave the country in less than 4 weeks who has not received a dose of IPV or bOPV in the previous 4 weeks to 12 months get a dose before leaving the country

Ensure documentation of polio vaccination on an International Certificate of Vaccination or Prophylaxis (ICVP)

7Clinical Update: Interim CDC Guidance for Travel to and from Countries Affected by the New Polio Vaccine Requirements and Recommendations

RABIES

Latin “Rabidus”… madness, rage “fury” • First known use in literature about 1598 • Family: “rod shaped” • Genus: “Lyssa virus” the Greek goddess or “daimona” (spirit) of madness, rage, frenzy • Bullet Shaped Virus RABIES • Acute Viral Infection • Almost always fatal • once symptoms develop

• At least 55,000 deaths/year • Death is gruesome in every respect • “Hydrophobia” • swallowing causes spasm of respiratory muscles and muscles related to swallowing • Frothy saliva is due to the inability to effectively swallow • The patient remains conscious of what’s happening until the end RABIES “IF BIT – TRIP OVER”

• , bats and other animals (cats in NJ) • Endemic in Asia, Africa, Central &

Pre-Exposure Evaluation • Risk of credible exposure • Mission, expedition travel, children

When bit: “WAR” 1. Wound Care 2. : HRIG - usually within 7 days 3. PRE Exposure Prophylaxis • Contact with wild or domestic animals • Remote areas where medical care is difficult to obtain/delayed • Longer than 4 weeks in an area where rabies is common • Three 1.0‐mL IM (deltoid area) of HDCV or PCEC vaccine • days 0, 7, and 21 or 28 • If not completed, not protected

Type Name Route Indications Human Diploid Imovax® Pre‐exposure or Cell Vaccine Intramuscular Rabies Post‐exposure (HDCV) Purified Chick Pre‐exposure or Embryo Cell RabAvert® Intramuscular Post‐exposure Vaccine (PCEC)

NEVER IN GLUTEALS • Pre‐exposure prophylaxis does not eliminate need for post exposure evaluation ‐ it eliminates need for HRIG and decreases number of doses of vaccine needed Rabies Vaccine: Post Exposure Prophylaxis

• Tetanus up to date (5 years) • If previously vaccinated: • Rabies Vaccine Only • Day: 0 and 3 • If never vaccinated: • HRIG (once) 20 IU/kg • Rabies Vaccine • Immunocompetent: days: 0, 3, 7and 14 • Immunocompromised: days: 0, 3, 7, 14 and 28 • And titer 7‐14 days post completion Most Deadly :

• gambiae • • : aegypti, albopictus • Dengue • • Yellow fever –alsoHaemagogus • • Zika • • Japanese Encephalitis • Various mosquito vectors • Filariasis, lymphatic Japanese Encephalitis Arbor • Mosquito: Culex species • Single Strand RNA : Closely Related to WNV and St. Louis Encephalitis

Endemic in most of Asia and western Pacific • most common vaccine‐preventable cause of encephalitis • Incubation: 5-15 days • <1% infected develop clinical symptoms • Fever, , vomiting progressing to neurological symptoms • are common Japanese Encephalitis

No specific treatment Hospitalization for supportive care Close observation is generally required

Outcome •Among patients who develop encephalitis, 20% ‐ 30% die •30%‐50% of survivors continue to have neurologic, cognitive, or psychiatric symptoms JE Vaccine Ixiaro (since March 2009) • inactivated culture–derived vaccine • 96% of adults developed protective neutralizing antibodies after receiving a primary immunization series of 2 doses administered 28 days apart • Rural areas > One month visit • 2 Doses IM day 0, day 28 • Completed >= 1 week before travel • Immunity wanes • 58%-83% at 12 months • each year if continued exposure Yellow Fever

• Mosquito-borne acute viral hemorrhagic disease • Transmitted primarily by infected Aedes (Africa) or (S. America) • Increases in Rainy season • S. America: Jan ‐ May • Africa: July –Oct • RNA virus ‐ genus Flavivirus • 7 : 2 in S. America, 5 in Africa

• Increasing incidence • , , population movements and

• 200,000 cases each year ‐ Nonspecific influenza like syndrome • Incubation period: 3‐6 days (range 2‐9) • ~15% go on to toxic form: • , hemorrhagic symptoms and multisystem organ failure • 30,000 deaths, each year (90% occurring in Africa) • is 20‐50% Yellow Fever 3 transmission cycles: Jungle (Sylvatic), Intermediate (Savannah), and Urban Yellow Fever

• Endemic in equatorial Africa and South America (>900 million population) • Estimated risk of illness and death for a 2‐week stay in endemic area • West Africa are 50/100,000 and 10/100,000, respectively • 500/million and 100/million for 2 week stay • South America are 5/100,000 and 1/100,000, respectively • 50/million and 10/million for 2 week stay

Yellow Fever Vaccine YF-VAX Only required vaccine • Valid 10 days after vaccine • May up to 6 days or deny entry • Valid for 10 years • Medical exemption does not guarantee country admission • Travelers aged >= 9 months • Effective immunity within 30 days for 99% of persons vaccinated • Effective against all 7 serotypes

Yellow fever vaccine is given to protect a person against the disease, as well as to protect against the spread of the disease among unimmunized people. Under the IHR, countries can require travelers to show proof of yellow fever vaccination to prevent importation and transmission of yellow fever virus. ACIP Yellow Fever Vaccine Recommendations • Single Dose YFV for most travelers

• Boosters • Definitely before next travel: if at risk • Pregnant when received initial dose • Hematopoietic stem cell transplant after initial dose • And are sufficiently immunocompetent • HIV: every 10 years

• May be given to travelers • whose last dose was >10 years ago and are traveling to • higher risk settings (e.g.: West Africa during peak transmission season) • areas with ongoing transmission outbreaks • prolonged stay in endemic areas

MMWR, June 19, 2015, Vol 64, #23 Yellow Fever Vaccine: Contraindications/Precautions

LIVE  Should not be given to primary immunodeficiency, transplant recipients, immunosuppressive and immunomodulatory therapies, or HIV patients with CD4 counts <200/ml, Age < 6 months, allergy to vaccine component (), / • YF & MMR should be given 30 days apart

Specific contraindications  thymus disorders

Precautions  May increase risk of MS exacerbations  Risk of serious vaccine effects > 60 years of age > 70 years of age Yellow Fever Vaccine: Serious Adverse Reactions

• Immediate hypersensitivity/anaphylactic reactions – • Desensitization regimen

• YF vaccine-associated neurologic disease (YEL-AND) – Rarely fatal – Onset 3-28 days – Several distinct clinical syndromes including: • , GBS, acute disseminated and bulbar palsy - Risk: general: 0.8/100,000 > 60: 2.2/100,000 Yellow Fever Vaccine: Serious Adverse Reactions

• YF vaccine-associated viscerotropic disease (YEL-AVD) • Mimics naturally acquired YF disease • Onset range: 1 – 8 days, average: 3 days • Death rate is 65% • Specific risk factors: > 60 years old, thymus disease or thymectomy • Risk: general: 0.3/100,000 >60: 1.2/100,000 > 70: 2.5/100,000

Both YEL-AND and YEL-AVD are seen in naïve only • All primary vaccinees must be told to call with symptoms of any kind within first week of vaccination • Any flu-like or febrile illness need CBC and CMP Yellow Fever Vaccine: Shortage • Began 2016 ‐ Worldwide • December 2015: Outbreak • Spread: DRC • January 2016: • Routine childhood immunization in Africa suspended • Emergency stockpiles diverted to Angola • March of 2016 –10 million doses • 1 million doses not efficacious • June 2016: WHO released fractional dose • 1/5 dose is good for 12 months • Civilian Supplies exhausted in US in 2017 • Restock not until 3rd or 4th qtr. 2018 Fractional YF‐VAX

For travel to a region of a country with risk of yellow fever, • Full dose or postpone trip • Critical if area of ongoing outbreak Fractional Dose: • 1/5 of the usual dose (0.1 ml instead of 0.5 ml) SQ • considered protective 10 days after it is administered • Can give full dose at later date

• considered protective for one year. Documentation: • No Yellow Card • Certificate of Medical Contraindication to Vaccination Stamaril

• Pasteur ‐ France • Used in 70 countries • Safety and Efficacy • Similar to YF‐Vax

• In US • Under an investigational new drug (IND) program • Available only to a limited number of clinics Hajj and Umrah

Umrah (February 2019) Hajj (August 2019)

Yellow Fever – 10 days before arrival Meningococcal quadrivalent – 10 days before arrival (<= 3 years) Polio – 6 weeks before arrival (adult) Influenza – before arrival – If is expired use Southern Hemisphere vaccine Influenza 1918: The Begins

The cook was Albert Gitchell at Camp Funston, KS • Reported for sick call on 11 March 2018 • c/o HA, sore throat, cough and high fever • By noon 107 other men reported the same symptoms

His friends traveled to Europe • Thus, Epidemic began • It would go on to kill ~ 20‐50 million people worldwide

General References

1. Vaccines 7th edition ‐Expert Consult; Stanley A. Plotkin, MD, Walter A. Orenstein, MD and Paul A. Offit, MD (2017) 2. Kroger AT, Duchin J, Vázquez M. General Best Practice Guidelines for Immunization. Best Practices Guidance of the Advisory Committee on Immunization Practices (ACIP) 3. Advisory Committee on Immunization Practices Recommended Immunization Schedule for Adults Aged 19 Years or Older —United States, 2018, MMWR/ February 9, 2018 / 67(5);158–160 Thank You