Travel and the Immunocompromised. ICH Meeting (11 th August 2015) Dr Ian Woolley

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1 Travel and the Immunocompromised ICH Meeting (11 th August 2015) Dr Ian Woolley

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3 Why is it interesting?

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5 Place Behaviour Immunity

6 all the world is divided into splitters and lumpers and in the end the splitters always win Oscar Ratinoff

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8 Travel is Common

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17 Boggild JTM 2004

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19 Not all travel is the same

20 Migration

21 190 patients ¾ from Latin America 36.8% (70 of 190) of the patients had at least one positive result for any parasitic disease (including Schistosomiasis, Chagas and intestinal parasites)

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26 VFR

27 3 patients who had stopped taking medication when travelling overseas - Poor healthcare structures - Stigma - Lack of privacy - Instability

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29 Tourism/Medical tourism/travelling for work

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33 Hemaglobinopathy Patients Premawardena et al (unpublished)

34 Premawardena et al (unpublished)

35 Premawardena et al (unpublished)

36 Malignant Haematology Contact with Wild or Exotic Animals Yes No Ate From Street Vendor Received Travel Advice Yes No Yes No Regular GP Yes No Diagnosed at Time of Travel Yes No Stage of Disease Local Advanced Chemotherapy Within 6 Months Over 6 Months Ago Never Patient Became Sick Overseas 4.5%(n=2) 4.5%(n=2) 2.3%(n=1) 6.8%(n=3) 5.3%(n=2) 2.6%(n=1) 6.8%(n=3) 2.3%(n=1) 2.3%(n=2) 2.3%(n=2) 2.6%(n=1) 6.8%(n=3) 2.3%(n=1) 4.5%(n=2) 2.3%(n=1) Patient did not Become Sick Overseas 4.5%(n=2) 83.4%(n=38) 25.0%(n=11) 65.9%(n=29) 47.4%(n=18) 44.7%(n=17) 90.0%(n=40) 0%(n=0) 45.5%(n=20) 45.5%(n=20) 34.1%(n=15) 56.8%(n=25) 36.4%(n=16) 38.6%(n=17) 15.9%(n=7) P-value P=0.020 P=0.914 P=0.608 P=0.025 P=1.000 P=0.611 P=0.379 Countries Visited High Income Middle Income Low Income 4.5%(n=2) 4.5%(n=2) 0%(n=0) 54.5%(n=24) 34.1%(n=15) 203%(n=1) P=0.822 Campion et al (unpublished)

37 What to do 1. Pre-immunosuppression screening 2. Boosting of immunity when appropriate 3. Talk about travel + refer when necessary (regular questionairre?) 4. Advise about behaviour 5. Avoid live vaccines where possible

38 SOT & vaccination Ideally start prior to transplant including for anticipated travel Pre-transplant immunity boosted after transplantation more effective than 1 o vaccination following transplantation Vaccination - start several months before trip, to allow time for boosters +/- serology Kotton et al., Am J Transplantation 2005; 5: 8 14

39 Allogeneic HSCT & vaccination Immune status of donor important for short-term transfer of immunity, & boosted by; Immunizing donor before transplant Early post-transplant vaccination of recipient with conjugate or protein based vaccines No transfer of donor immunity or boost by vaccination for polysaccharide vaccines

40 Killed or conjugate vaccines are Hepatitis A safe Hepatitis B Typhoid injectable Hib Influenza Meningococcal Polio (injectable) JE (Jespect) Pneumococcal Rabies Diphtheria/Tetanus/Pertussis

41 but effective in the immunocompromised? Influenza Pneumococcal

42 HIV Transient increases in viral load observed after influenza, tetanus, pneumococcus, hepatitis B, cholera and rabies vaccination Influenza Response to vaccine reduced but still good protection even if CD4 < /L Pneumococcal disease 23-valent polysaccharide vaccine: reduced response, but still has protective efficacy Consider using conjugate vaccine Prevenar if possible

43 Plan early! 6 months prior! Change itinerary Check Hep A, B immunity Pre (+ post) Quantiferon Gold TB Avoid live vaccines YF, MMR, VZV, BCG, Oral polio, Oral typhoid Immunize Before immunosuppression esp Hep A, B, DTP-Polio, MMR After CD4 count > 200 in HIV Increased / extra doses may be required Check response Hep A, B Disease (+ medication) Mx Plan Screen if history of exposure in high prevalance country to Tb, Schistosomiasis etc

44 Hep A vaccine 6 Dutch travel clinics Variety of immunosuppression MTX 33% Azathioprine 23% Anti-TNF alpha 18% Steroids (alone) 15% Van den Bijllaardt JTM 20 (5):

45 Hep A vaccine in immunosuppressed Protective antibodies 1 dose 60% 2 doses 95% Normally 98% >99% Van den Bijllaardt et al JTM 20 (5): May need two doses of vaccine prior to departure!

46 SOT & Hep A vaccine 1 o dose 2 nd dose 2 yrs later Liver 41% 97% 59% Renal 24% 72% 26% Rapid antibody decline 2 years after vaccination! Pooled immunoglobulin im 85 90% effective? Gunther et al., Transplantation 2001; 71: ; Kotton et al., Am J Transplantation 2005; 5: 8 14

47 Meningococcus: polyvalent conjugate vaccines titers 8 higher with MenACWY-CRM (Menveo) vs MCV4-D(Menactra) But no data in immunosuppressed! MenACWY-CRM MCV4-D Percentage of subjects with hsba 1:8 Serogroup Jackson LA, et al. Clin Infect Dis. 2009;49:e1-e10.

48 JE Vaccines JESPECT killed vaccine is OK IMOJEV: Live vaccine chimeric virus YF vaccine virus expressing JE antigens No data: avoid

49 MTX/Azathioprine & live vaccines Generally C/I Off MTX/Aza 3 mths prior & 2 weeks post

50 Steroids: depends on dose Live vaccines C/I if >20mg Prednisolone/day for > 2 weeks US guideline >10mg Prednisolone/day British & French guideline If just coming off high dose steroids wait 4 weeks

51 Live vaccines

52 Individualised risk assessment - & not just vaccination

53 Food/Water Insect Animal bite Accident road/water Sun exposure Sex Insurance Psych/Cultural Prevention other than vaccines/antimalarials Travel appointment is not just about the jabs

54 Traveller s Diarrhoea Prevention - Avoid antacids! If severe - seek medical attention! Self treatment Norfloxacin few interactions Azithromycin - transient increase cyclosporine, tacrolimus levels Kotton Am J Transplantation 2009; 9 (Suppl 4): S273 S281

55 Malaria Kotton et al., Am J Transplantation 2005; 5: 8 14

56 Malaria Safest in rheum pts but expensive Neuropsychiatric symptoms Increase cyclosporin levels Photosensitive rash (caution in SLE?) Increases MTX toxicity Kotton et al., Am J Transplantation 2005; 5: 8 14

57 Drug-drug interactions Macrolides Chloroquine Doxycycline Mefloquine Primaquine May all increase levels of calcineurin inhibitors Kotton Am J Transplant 2013

58 Insurance Cover for pre-existing conditions May be expensive, or declined Government reciprocal health agreements: Belgium Denmark Finland Ireland Italy Malta Netherlands New Zealand Norway Slovenia Sweden United kingdom humanservices.gov.au/customer/services/medicare/reciprocal-health-care-agreements

59 Medication Avoid medication changes shortly before travel Ensure no side effects/complications occur while travelling Carry oversupply of medications, with prescriptions Divide bn carry-on & checked baggage Long term travel/obtaining supplies overseas Restrictions variable & inconsistent eg codeine Original packaging/ Drs letter

60 Plan early! 6 months prior! Change itinerary Check Hep A, B immunity Pre (+ post) Quantiferon Gold TB Avoid live vaccines YF, MMR, VZV, BCG, Oral polio, Oral typhoid Immunize Before immunosuppression esp Hep A, B, DTP-Polio, MMR After CD4 count > 200 in HIV Increased / extra doses may be required Check response Hep A, B Disease (+ medication) Mx Plan