Pre-travel Advice in the High Risk Patient

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Pre-travel Advice in the High Risk Patient Obi Nnedu MD, MPH, Ctropmed, CTH Infectious Diseases Department October 27, 2017 Disclosures None 1

Objectives Provide a broad overview of the elements of a pre-travel visit. Discuss issues related to special patient populations Pre-travel encounter Advice and education Immunizations Pre-Travel visit Prescriptions -Past medical history -Itinerary -Accommodation -Planned activities -Behavior 2

Advice and education Avoid traveling to remote areas that are far from any medical care Check with insurance company to see if coverage applies at destination. If not, consider additional insurance Consider purchasing evacuation insurance Advice and education Don t get hit Don t get bit Don t get lit Don t do it Don t eat s**t (avoid motor vehicle accidents) (avoid mosquito/tick/animal bites) (avoid excessive alcohol use) (avoid casual sex) (avoid eating contaminated food) Borrowed from Dr. Jay Keystone, University of Toronto 3

Immunizations Routine Recommended Required MMR Hepatitis A Yellow Fever Influenza Hepatitis B Meningococcal vaccine Polio Japanese encephalitis Polio Tetanus/Pertusis/Diptheria Typhoid Pneumococcus Meningococcal Varicella Zoster Hib Hepatitis A Hepatitis B Prescriptions Malaria prophylaxis? Over the counter antibiotic for severe diarrhea? Altitude sickness medications? Prescription home medications? 4

Case 1 36 y/o flight attendant with a history of HIV diagnosed 10 years prior. He is currently stable on Truvada and dolutegravir. Viral load is below 40. His CD4 count is 270. He has never had any opportunistic infections and doesn t take any other medications besides HAART. The Airline he works for wants him to start working on the routes got to Brazil. Per their policy this will require him to get the yellow fever vaccine. What advice should you give him? Salit IE et al. JAMC. 2005 5

Salit IE et al. JAMC. 2005 6

Yellow fever Live vaccines and immunocompromised patients Live vaccine Live influenza vaccine HIV <200 HIV >200 SOT SCT Asplenia Biologics X X X X U X MMR X U X C 1 U X Oral Typhoid X X X X U X Varicella X C X C 1 U X Zoster (shingles) X C X X U X Yellow fever X U X X U X C 1 =Start 2 years post SCT if they are not on immunosuppression and don t have GVHD X=contraindicated C=consider U=use as indicated 7

Risk of malaria among HIV infected persons Incidence of malaria among HIV+ vs HIV- adults Study Patnaik et al, JID. 2005. Whitworth J, et al. Lancet. 2000. Findings HR=2.7(1.2-6.1) OR=1.8(1.4-2.3) Risk of malaria among HIV infected persons Incidence of malaria among CD4<200 vs CD4>500 Study Findings Laufer MK, et al. JID. 2006 IRR=1.9(1.1-3.3) French N, et al. AIDS. 2001 IRR=4.0 p=0.001 8

HIV and malaria prophylaxis Drug Protease inhibitors NRTIs NNRTIs Integrase and entry inhibitors Mefloquine Levels of PIs None None Mefloquine levels with cobisistat/elvitegravir Malarone Levels of malarone None Efavirenz levels of malarone None Doxyxycline None None Not studied None Chloroquine None None None None Primaquine None None Not studied None Case 2 A 26 y/o female charter school teacher presents to clinic for pretravel consultation prior to going to traveling to the Amazon forest in Brazil. She is doing well and denies any medical problems. At her pre-travel visit, you counsel her about yellow fever, zika, dengue, malaria, gastrointestinal infections. Yellow fever vaccine, Typhoid IM vaccine, Hepatitis A vaccine are ordered. You update her influenza and tetanus vaccinations. Malarone is prescribed for malaria prophylaxis and Azithromycin is prescribed for use in the event of severe diarrhea. 9

Case 2 4 weeks later, she calls your clinic and states that she just found out from her OB/GYN that she is pregnant. Her OB/GYN estimates that she is about 8 weeks gestational age What should you do? 10

Pregnancy and yellow fever vaccination 4 studies identified that reported outcomes of yellow fever vaccination of pregnant women Total number of pregnant women in these studies was 1351 There were no serious adverse events reported among these women Rate of congenital abnormalities were the same in vaccinated group as compare to the general population Pregnancy and vaccinations All live vaccines are contraindicated in pregnant women with the exception of yellow fever vaccine Yellow fever vaccine may be given to a pregnant woman if travel is deemed necessary and the risk of yellow fever acquisition outweighs the potential risk of administering the vaccine Typhoid intramuscular vaccine is believed to be safe in pregnancy but there is not enough data 11

Pregnancy and malaria 12

Malaria cases in the U.S. in 2014 1724 confirmed malaria cases in the U.S.A. 631 cases were in females. 32 (5.1% of women) were pregnant. 12 of the pregnant women provided information on malaria prophylaxis. 11 of them did not use any chemoprophylaxis Pregnancy and malaria prophylaxis Drug Dosage Duration Pregnancy Atovoquone-Proguanil 1 adult tablet (250/100mg) daily Start: 1 day before travel. End: 1 week after return. Chloroquine base 300mg once a week. Start: 1 week before travel. End: 4 weeks after return. Mefloquine Doxycycline 1 adult tablet (250mg) once a week. 1 adult dose (100mg) once a day. Start: 1 week before travel. End: 4 weeks after return. Start: 1 day before travel. End: 4 weeks after return. Avoid Safe Safe Avoid 13

Zika virus Modes of Transmission -Mosquito -Sexual intercourse Pregnancy and zika virus in the U.S.A. From 2015 to 2017 1993 total completed pregnancies with or without birth defects among women with confirmed zika virus infection 98 Live born infants with birth defects 8 pregnancy losses with birth defects 14

Women traveling to a zika endemic area should avoid conceiving a child within 2 months of return Men traveling to a zika endemic area should avoid conceiving a child within 6 months of return Pregnant women living in non-endemic areas should avoid non-essential travel to endemic areas A spouse who has traveled to a zika endemic area should consistently use condom use or practice abstinence with his pregnant wife 15

Hepatitis E and pregnancy Hepatitis E and pregnancy Transmitted via fecal oral route (primarily through contaminated water sources) Case fatality rate among pregnant wound is 10-30%. Among non-pregnant individuals it is 1% Pregnant women should be advised to drink bottled water. Boiling water and chlorination also deactivate the virus 16

Case 3 54 y/o male originally from India with a history of hepatitis C s/p liver transplantation in 2014, CMV R+D+. Initial post transplant course complicated by intraabdominal hemorrhage requiring surgical removal of hematoma. He also had a traumatic thoracentesis that led to a hemothorax Otherwise he has no history of liver rejection He is currently on prograf 1mg in the morning and 0.5mg in the evening Case 3 He came to travel clinic for pre-travel consultation. He will be visiting friends and relatives in the Punjabi region of India. He plans to stay there for 60 days. How should this patient be approached? 17

Case 3 Advice and education Immunizations Pre-Travel visit Prescriptions -Past medical history -Itinerary -Accommodation -Planned activities -Behavior 18

Advice and education Timing of travel: Travel overseas within 1 year of organ transplantation should be discouraged Risk of most travel associated infections are higher among SOT patients. Specifically respiratory infections, gastrointestinal infections and mosquito borne infections Access to and quality of medical care at destination Immunizations and Solid Organ transplant Review vaccination history. If patient doesn t remember and there is no record of vaccination, check titers if possible. Live vaccines are contraindicated. If a live vaccine is needed consider passive immunization (IVIG) were available. 19

72 papers included in this review Solid organ transplant patients mounted lower immune responses to most vaccines as compared to controls Sero-conversion rates were lower for hepatitis A and hepatitis B among solid organ transplant patients as compared to control Antibody titers appear to decline over time for some vaccines (hepatitis A, hepatitis b, pneumococcal) Heterogeneity of the studies limits the ability to draw strong conclusions from this review article 20

Immunization and Solid Organ transplant Danziger-Isakoff L, et al. Am J Transplant. 2013. Immunizations and Solid organ transplant 21

Prescriptions Travel Med Mefloquine Atovoquone-proguanil Doxycycline Chloroquine Fluoroquinolones (FQ) Azithromycin Rifaximin Calcineurin inhibitors (Tacrolimus, Cyclosporine) Possible increase in calcineurin levels. Prolonged QT No data Possible increase in calcineurin levels Possible increase in calcineurin levels. Prolonged QT Possible prolonged QT. Possible increased FQ levels Possible increase in calcineurin levels No data Prescriptions Always notify the patient s transplant coordinator when new prescriptions are being made. Notify the patient s transplant coordinator about vaccinations given to the patient. 22

Case 3 Serologies confirming immunity to hepatitis a, hepatitis b, measles, mumps and rubella were obtained I opted against checking serologies for pneumococcal vaccine. Instead, I gave him prevnar13 He received the typhoid intramuscular and Tdap vaccination Prescription for malarone for malaria prophylaxis and Azithromycin for use in severe diarrhea were provided Questions Email: onnedu@ochsner.org Phone: 504-842-4005 23