Page 1. A) Mefloquine B) A tour of Cusco and Macchu Picchu C) Scuba Diving D) Azithromycin

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1 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 Page 1

2 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 1 st trimester - miscarriage risk 2 nd trimester - safest 3 rd 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. Page 2

3 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 Page 3

4 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 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 Page 4

5 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. Page 5

6 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 proteaseinhibitor 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 Page 6

7 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 anticytokines (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 Page 7

8 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 PPSV 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, 2 nd 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 Page 8