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Speakers must disclose all associations with proprietary entities that may have a direct relationship to the subject matter of their presentation.  

Dr. Freedman has returned a disclosure form indicating the following affiliations or financial interests in the last 3 years:

• Grant Support• Centers for Disease Control and Prevention

• Shoreland, Inc

• Honoraria, Consulting, or Writing Fees• Antimicrobial Therapy, Inc

• Shoreland Travax

• UptoDate, Inc

A) Mefloquine

B) A tour of Cusco and Macchu Picchu

C) Scuba Diving

D) Azithromycin

Children Pregnant HIV Other Immunocompromised

Immunosuppresive meds, transplants, malignancy

Chronic Disease Diabetes, renal, hepatic, cardiopulmonary

Most recommendations based on anecdote

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Vaccine – preventable disease

Malaria

Travelers diarrhea

Other stuff

Air travel

Altitude and depth

Concrete plan for obtaining medical care at destination

Vaccines

Malaria

Use of common travel-related medications

1st trimester - miscarriage risk

2nd trimester - safest

3rd trimester - premature labor & complications

Any pregnancy high-risk factor precludes travel

Destination substantially beyond control of MD

Pre-travel U/S

A)Yellow Fever

B) MMR

C) Japanese encephalitis (vero‐cell)

D) Rabies

Little safety data for any vaccine

Contraindicated

MMR, varicella, Ty21a, live influenza

Killed influenza wait till 2nd trimester in many countries

Not USA

Avoid unnecessary vaccines but

Case by case – if risk high enough any other vaccine can be given

In USA CDC will provide consultation and YF titres

A distinguished panel representing authoritative institutions from North America and Europe found no evidence of adverse pregnancy outcomes for the inactivated vaccines reviewed

The benefits of vaccinating pregnant women generally outweigh the potential risks if the woman is at risk of exposure to an infection that would pose a risk to her fetus.

No evidence of adverse pregnancy outcomes from immunization of pregnant women with  inactivated vaccines reviewed: influenza, meningococcal, and tetanus toxoid including Tdap and Tdap/IPV).

There is substantial evidence in the literature, and no evidence to the contrary, of the safety of the 5 live vaccines reviewed (rubella, measles, mumps, poliomyelitis, and yellow fever).

Inadvertent vaccination with a live vaccine is not an indication for termination of pregnancy.

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Emphasize personal protection against arthropods; DEET okay

Malaria infection increases fetal loss

Malaria increases maternal mortality

Rx – choroquine or quinine preferred

Mefloquine now FDA approved

Artemisinins--1st trimester concern

Malarone, doxycycline, primaquine-No

MFQ: probably safe in all 3 trimesters US FDA labeling now Cat. B (2011)

Malarone, Doxycycline – contraindicated

Chloroquine, proguanil safe

High risk travel; define case-by-case Official WHO recommendation:

Don’t go to chloroquine resistant areas

If MFQ refused then advise trip cancellation

No flying after 35 wks

Need to check policy airline by airline

No trekking over 7,000 feet

No diving

Avoid as many meds as possible

ORS

Loperamide probably okay

Antibiotics: avoid in general, azithromycin okay

Metronidazole now considered safe

DEET, pyrethroids

Acetazolamide contraindicated

Iodine resin in water filters

No contraindication to any vaccine even live Except Yellow fever--new data from Brazil No protection of infant by vaccinating mother

Mefloquine, chloroquine okay Insufficient data on doxy, atov/prog, primaquine No protection of infant provided by milk

Travelers diarrhea Mother needs extra fluid intake

Menstrual problems

Absent periods

Irregular periods

Heavy periods

Contraception

“Morning after” strategies

Vaginal infections

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A 9‐month old infant is traveling to a rural area of southwestern China to stay with his grandparents for 6 months during summer and fall. Which of the following vaccines is indicated at the time of the visit?

A) Hepatitis A

B) Tick‐borne encephalitis

C) Measles

D) Typhoid Vi polysaccharide

Accelerate DTaP, polio, PCV, Hib, Rotavirus Start at 6 wks and space by 4 weeks X 3 4th dose polio

YF after 9 months; 6 months exceptionally Mouse-brain Jap B contraindicated JE-VC now used

Ineffective: meningococcal polysaccharide, typhoid Vi, Ty21a, Hepatitis A; likely effective but no guideline <1yr

ACIP needle gauge/length guidelines

Early MMR or measles for travel between 6-12 months of age

Not countable; revaccinate according to standard 2 dose-regimen

>12 months of age – 2 doses at least one month apart

Thus 2 countable doses; don’t repeat at school entry

• EMA licensed 2013/ACIP 2013– 6 µg/0.5 mL dose (regular adult dose)

for ≥ 3 years and a 3 µg/0.25 mL dose (half adult dose) 2 months to 2 years.

– 2 doses 28 days apart.– Pediatric data: Vaccine 2010; 28:834-9

>4 yr – 2 MMR on board, DTaP booster

<5 yr – poor meningococcal polysaccharide respons

Use MCV4 if available (>9 yrs months)

JE-VC (adult dose)

Can’t swallow Ty21a capsules

Tdap at age 11 per ACIP

Different pediatric doses

HepA, HepB, JE (mouse brain), Influenza (under age 3)

More susceptible

Breast-feeding

ORS in infants, toddlers

> 3 yr - loperamide & antibiotics are okay

Azithro tabs (suspension doesn’t travel)

2004-ciprofloxacin FDA approved for children

Pediatricians & different etiology of TD compared to developed world diarrhea

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Official WHO recommendation:Infants and young children to avoid travel to malarious areas, especially if chloroquine resistant

Mefloquine even in infants Crush tablets in chocolate syrup

Malarone; pediatric tablets; >5kg

Chloroquine syrup overseas

Doxycycline only >8 yrs

Sedatives not recommended Dimenhydrinate but do test dose

Child Restraint Seat (CRS) Rules vary by airline; FDA approved CRS

Accident prevention CRS needs a seat-belt in the car! Accommodation often not child proofed Drowning, drowning, drowning

Letter from non-accompanying parent Carry several wallet-size photos of each child at

all times

Divided into 4 categories Severe Immunocompromise (non-HIV) Severe Immunocompromise (HIV) Asymptomatic HIV Chronic diseases with limited immune deficits

New “biological” drugs Now >40 agents approved Many modes of action, variable and unknown

immunosuppressive effect Guidance empirical; most are cautious

Immunocompromised travelers made up 1.2% of travelers seen in U.S. travel clinics.

These travelers pursued itineraries similar to those of immunocompetent travelers.

Immunosuppressive medication and HIV infection were the most common causes of immune suppression.

The value of pre-travel advice given to immunocompromised travelers remains to be assessed.

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Main risk is exacerbation of underlying disease condition

Disease risks at destination More severe outcomes in that traveler?

Proposed preventive interventions Safe? Less effective?

Finally does traveler understand wisdom of proposed itinerary?

Persons living with HIV should not automatically be equated with truly immunocompromised patients. Generally, HIV-infected travelers are on ongoing modern anti-retroviral regimens tailored to completely suppress viral replication to undetectable levels. HIV infected-individuals who have no replicating virus are no longer thought to be immuno-compromised regardless of CD4 cell count.

PCV13 then PPSV23 in all Avoid live antigens if possible

Measles, varicella if <200 CD4 or OI, Ty21a in all; alternative available YF if indicated but CDC now more cautious Case by case if CD4 <500; never if <200 Viral load may be better determinant

May be refused entry to country; DOS web Consider prophylactic quinolones

Intense food/water precautions

Difficulty in obtaining medical care

Immunization with YF vaccine produces a protective titer of antibodies in 98% of patients infected with HIV.

Poor and early-waning responses are associated with high or uncontrolled viral loads, rather than with low CD4-T cell counts.

Safety of YF immunization in HIV-infected patients still not properly studied.

If at all possible wait for immune reconstitution by starting ART and then vaccinating.

Immunity may wane, definitely need the 10-year booster

Doxycycline and chloroquine are the least likely antimalarials to have interactions with HAART.

Mefloquine is the most likely prophylactic antimalarial to have potential interactions and it may be prudent to avoid mefloquine, if possible, in patients on HAART.

The extremely cautious patient might want to avoid atovaquone/proguanil if on a protease-inhibitor or on a NNRTI although no clinical prophylaxis failures have been demonstrated.

PIs are the most likely to have interactions with antimalarials, whereas NRTIs and integrase inhibitors are the least likely.

Combinations of integrase inhibitors with NRTIs have no interactions (except elvitegravir/cobicistat may theoretically increase mefloquine levels.

Atripla with chloroquine, mefloquine, or doxycycline appears to be acceptable

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Atripla-efavirenz component may decrease plasma concentrations of proguanil. Theoretical, discuss with patient.

PIs such as Kaletra (lopinavir/ritonavir) : Favor doxycycline avoid chloroquine and mefloquine due to possible QT

prolongation Kaletra may lower the atovaquone and proguanil levels

(considered a minor interaction).

Clear compromise (don’t travel much) Leukemia, lymphoma, disseminated malignancy,

current chemoRx/XRT, bone-marrow transplants, organ transplants

No live antigens; food/water precautions

Medication-related compromise See next slides for agents

No live antigens; increased risk of travel-related infection

Three Issues: 1) Vaccine Safety; 2) Vaccine Efficacy;3) Susceptibility to infectious diseases

• No live vaccines, increased risk of infection• Most recommendations take cautious

approach due to lack of safety data– Treat immunomodulatory drugs same as

immunosuppressants– Same policy for 2014 CDC Yellow Book

• Listing that follows• Excludes: drugs and agents only used for cancer and anti-

cytokines (uncommonly used at present)

• Glucocorticoids (≥20 mg/day of systemic prednisone or equivalent for ≥14 days). 

• Alkylating agents– Cyclophosphamide

• Antimetabolites– Methotrexate, Azathioprine, 6‐mercaptopurine, Leflunomide

• Transplant‐related immunosuppressive agents– Cyclosporine, Tacrolimus, Sirolimus, Mycophenolate mofetil, Muromonab (Anti‐CD3)

• TNF blocking Agents– Etanercept (shorter half life), Infliximab, Adalimumab, Certolizumab, Golimumab

• Lymphocyte depleting drugs (***within last 1 year)

– Rituximab, Alemtuzumab (CAMPATH), Alefacept, Antithymocyte globulin

• Adhesion blocking Agents– Ipilimumab, Abatacept

• IL-1 Blockers– Anakinra, Rilonacept, Canakinumab

• Interferons– Interferon-alpha, Interferon-beta 1a, Interferon-beta 1b

• MS only immunomodulators– Glatiramer, Natalizumab, Mitoxantrone, Fingolimod

Partial immunocompromise

Splenectomy, renal disease, hepatic disease, diabetes

Usual vaccination strategies; increased risk of infection

Add Hib (1 dose age >7yr), meningococcal (2 doses),pneumococcal (PCV13 then PPSV23 8 weeks later) if splenectomized

Spacing issues between PCV13 and MCV4)

Normal hosts

Replacement steroids, alternate day steroids, short course steroids (<2wks), intra-articular steroids, leukemia in remission off Rx >3mos

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FDA licensed early 2012 > 50 years

Prevnar 13 (Single dose). (=Prevenar)

ACIP September 2012 Focus on ALL adult (18-64) compromised hosts

PCV13 (Prevnar) then PPSV23 (Pneumovax) 8 weeks later Complicated guidelines for those with previous Pneumovax

Need at least 1 year after Pneumovax dose to give Prevnar

ACIP 2014 PCV for routine use >65 yrs PCV13 then PPSV23 6-12 months later

Need at least 1 year after Pneumovax dose to give Prevnar

Compromised: Administer 1 dose of PPSV23 at age 2 through 64 years, 2nd dose 5 years later No additional PCV13 doses for children

No disease specific data for most conditions

Need to know ongoing meds

More often the meds than the disease

Avoid live antigens

GI risk: Consider prophylactic quinolones

Copies of prescriptions

Plan for obtaining medical care