1. NY/NJ AETC Stuart Haber, MD EMPORIATRIC MEDICINE AND THE HIV-INFECTED TRAVELER

2. NY/NJ AETC Stuart Haber, MD ISSUES FOR ALL TRAVELERS Generally want at least 4-6 week lead time prior to departure to assess travel needs, especially vaccines and need for malaria chemoprophylaxis Generally want at least 4-6 week lead time prior to departure to assess travel needs, especially vaccines and need for malaria chemoprophylaxis Get list of medical clinics from IAMAT www.iamat.org Get list of medical clinics from IAMAT www.iamat.org www.iamat.org Bring 30-35% DEET spray where biting insects are anticipated Bring 30-35% DEET spray where biting insects are anticipated Avoid piercings and tatoos, acupuncture, even shaving by a barber in many of these developing areas Avoid piercings and tatoos, acupuncture, even shaving by a barber in many of these developing areas Be cautious of motor vehicle travel Be cautious of motor vehicle travel Swim only in chlorinated water Swim only in chlorinated water Health insurance: both international insurance(try credit card companies, yellow pages, internet) and air ambulance insurance: www.airambulancedirectory.com Health insurance: both international insurance(try credit card companies, yellow pages, internet) and air ambulance insurance: www.airambulancedirectory.comwww.airambulancedirectory.com

3. NY/NJ AETC Stuart Haber, MD SPECIFIC PRECAUTIONS FOR ENTERITIS Developing countries: especially important in patients with severe immunosuppression Developing countries: especially important in patients with severe immunosuppression Food and waterborne diseases:same precautions for all travelers regardless of HIV serostatus Food and waterborne diseases:same precautions for all travelers regardless of HIV serostatus If you can’t boil it, peel it, cook it, then forget it!! If you can’t boil it, peel it, cook it, then forget it!! No tap water, ice cubes. Bottled water, including for brushing teeth! No tap water, ice cubes. Bottled water, including for brushing teeth! Portable water purifiers ( with absolute one micron filter) Portable water purifiers ( with absolute one micron filter)

4. NY/NJ AETC Stuart Haber, MD TRAVELER’S DIARRHEA If traveler’s diarrhea is severe: must seek medical attention (gi bleeding, fever, vomiting, prostration) If traveler’s diarrhea is severe: must seek medical attention (gi bleeding, fever, vomiting, prostration) Enterotoxigenic E. coli probably no different in it’s presentation, but Salmonella, Campylobacter, Shigella can be worse in HIV+ people Enterotoxigenic E. coli probably no different in it’s presentation, but Salmonella, Campylobacter, Shigella can be worse in HIV+ people Occasional microsporidia(J Travel Med 1999 Dec;6(4):223- 7), enteroaggregative E. coli(CID 2001 Jun 15;32(12):1706-9), and Cryptosporidia Occasional microsporidia(J Travel Med 1999 Dec;6(4):223- 7), enteroaggregative E. coli(CID 2001 Jun 15;32(12):1706-9), and Cryptosporidia Other causes of enteritis eg,Cyclospora, Isospora belli, helminths, C. difficile, tropical sprue Other causes of enteritis eg,Cyclospora, Isospora belli, helminths, C. difficile, tropical sprue Treatment for uncomplicated disease:cipro 500mg BID for three to seven days with first day imodium. Treatment for uncomplicated disease:cipro 500mg BID for three to seven days with first day imodium.

5. NY/NJ AETC Stuart Haber, MD SELF-MEDICATION FOR OTHER AILMENTS Options of self-medication: for respiratory tract infection, sinusitis, otitis media,UTI, cellulitis Options of self-medication: for respiratory tract infection, sinusitis, otitis media,UTI, cellulitis

6. NY/NJ AETC Stuart Haber, MD INTERNATIONAL SCREENING OF TRAVELERS FOR HIV INFECTION Primarily aimed for those with extended stays: work visas, students Primarily aimed for those with extended stays: work visas, students Approximately 50 countries may block entry of HIV+ travelers Approximately 50 countries may block entry of HIV+ travelers Check with consular office(s) or go to www.travelstate.gov/hivtestingreqs.html Check with consular office(s) or go to www.travelstate.gov/hivtestingreqs.html www.travelstate.gov/hivtestingreqs.html Our own calls to Brazilian, Canadian, and British consulates did not bear out any refusal to have HIV+ travelers in their nation for short-term stay. However, long- term stay decided on case by case basis. Our own calls to Brazilian, Canadian, and British consulates did not bear out any refusal to have HIV+ travelers in their nation for short-term stay. However, long- term stay decided on case by case basis.

7. NY/NJ AETC Stuart Haber, MD TIMING OF HAART ACROSS TIME ZONES Take more doses in the period than less. Take more doses in the period than less. East to West: extra dose of Nukes, viramune and PIs at bedtime East to West: extra dose of Nukes, viramune and PIs at bedtime West to East: extra dose next morning West to East: extra dose next morning Efavirenz doesn’t need an extra dose (G. Moyle, personal comm.) Efavirenz doesn’t need an extra dose (G. Moyle, personal comm.) Viread has long intracellular half-life and may not need an extra dose Viread has long intracellular half-life and may not need an extra dose Debatable what to do with indinavir with respect to risk of nephrolithiasis Debatable what to do with indinavir with respect to risk of nephrolithiasis

8. NY/NJ AETC Stuart Haber, MD DRUG AND MEDICAL CARE ISSUES Adequacy of supply of medications, including need for refrigeration and avoidance of damp places Adequacy of supply of medications, including need for refrigeration and avoidance of damp places Adequacy of medical care in destination, especially important in prolonged stays-consult with IAMAT Adequacy of medical care in destination, especially important in prolonged stays-consult with IAMAT Avoid if possible, new medication changes just prior to travel Avoid if possible, new medication changes just prior to travel

9. NY/NJ AETC Stuart Haber, MD MALARIA PREVENTION Same precautions and prophylaxis with all travelers Same precautions and prophylaxis with all travelers Review itinerary on www.cdc.gov malaria site Review itinerary on www.cdc.gov malaria sitewww.cdc.gov Disease presentation not different in HIV, except more severe in HIV-positive pregnant women Disease presentation not different in HIV, except more severe in HIV-positive pregnant women Mosquito bite prevention with 30-35% DEET, bed netting, permethrin spray, and avoidance of dusk to dawn exposure Mosquito bite prevention with 30-35% DEET, bed netting, permethrin spray, and avoidance of dusk to dawn exposure Drug interactions: mefloquine had variable effects on ritonavir, with decrease in Cmax, Cmin, AUC. Despite strong inhibition of CYP3A4, mefloquine levels were not affected by ritonavir (Khaliq et al, 7 th Conf on Retro, abstract 92, 2000) Drug interactions: mefloquine had variable effects on ritonavir, with decrease in Cmax, Cmin, AUC. Despite strong inhibition of CYP3A4, mefloquine levels were not affected by ritonavir (Khaliq et al, 7 th Conf on Retro, abstract 92, 2000) Malarone: Proguanil AUC increased possibly via CYP 2D6, Atovaquone AUC may be decreased in presence of Ritonavir, mechanism unknown (Karp, Current Inf Dis Rep 2001, 3:50-8) Malarone: Proguanil AUC increased possibly via CYP 2D6, Atovaquone AUC may be decreased in presence of Ritonavir, mechanism unknown (Karp, Current Inf Dis Rep 2001, 3:50-8) Despite these observations, there are currently no dose adjustments recommended at this time. Despite these observations, there are currently no dose adjustments recommended at this time. Measure patient’s glucose-6-phosphate dehydrogenase level prior to trip (possible need for primaquine) Measure patient’s glucose-6-phosphate dehydrogenase level prior to trip (possible need for primaquine)

10. NY/NJ AETC Stuart Haber, MD MALARIA TREATMENT Quinidine:AUC increased by ritonavir via CYP3A4 inhibition. Quinidine reserved for severe malaria and decrease in maintenance rate of drug required. Quinine probably increased to lesser extent and should be avoided (risk of prolonged QT interval with Torsades de pointes) Quinidine:AUC increased by ritonavir via CYP3A4 inhibition. Quinidine reserved for severe malaria and decrease in maintenance rate of drug required. Quinine probably increased to lesser extent and should be avoided (risk of prolonged QT interval with Torsades de pointes) Treat non-severe malaria with malarone 4 pills/day for three days, or with lariam (increased risk of seizures). Treat non-severe malaria with malarone 4 pills/day for three days, or with lariam (increased risk of seizures). Self-treatment not generally advised Self-treatment not generally advised

11. NY/NJ AETC Stuart Haber, MD VACCINE ISSUES IN HIV+ TRAVELER Potential exposure to pathogen Potential exposure to pathogen Potential increase in side effects to vaccine Potential increase in side effects to vaccine Potential decreased efficacy of vaccine Potential decreased efficacy of vaccine

12. NY/NJ AETC Stuart Haber, MD VACCINES In most developing areas of world, following vaccine-preventable illnesses are addressed: In most developing areas of world, following vaccine-preventable illnesses are addressed: MeaslesMeasles Hepatitis AHepatitis A Typhoid FeverTyphoid Fever InfluenzaInfluenza Yellow feverYellow fever Hepatitis BHepatitis B PolioPolio Japanese encephalitisJapanese encephalitis RabiesRabies CholeraCholera MeningococcusMeningococcus

13. NY/NJ AETC Stuart Haber, MD VACCINES Killed (inactivated): Hepatitis A, Inactivated Polio (IPV), Rabies, Japanese encephalitis Killed (inactivated): Hepatitis A, Inactivated Polio (IPV), Rabies, Japanese encephalitis Live (attenuated): MMR, Yellow fever, oral Typhoid Live (attenuated): MMR, Yellow fever, oral Typhoid Subunit: Hepatitis B Subunit: Hepatitis B Polysaccharide: Pneumococcal, Meningococccal, Typhoid Vi Polysaccharide: Pneumococcal, Meningococccal, Typhoid Vi Split antigen: Influenza Split antigen: Influenza

14. NY/NJ AETC Stuart Haber, MD MEASLES VACCINE Increased prevalence of disease in SE Asia, Africa (especially sub-Saharan) based on W.H.O. data on measles in children Increased prevalence of disease in SE Asia, Africa (especially sub-Saharan) based on W.H.O. data on measles in children Worse disease with increased morbidity and mortality in HIV-infected people with pneumonitis and also encephalitis. Worse disease with increased morbidity and mortality in HIV-infected people with pneumonitis and also encephalitis. Increased risk of vaccine side effects in severely immunosuppressed: one known death in patient with AIDS and deaths in other immunosuppressed recipients. Increased risk of vaccine side effects in severely immunosuppressed: one known death in patient with AIDS and deaths in other immunosuppressed recipients. Vaccine considered safe in adults if T-helper count >200 &/or T-helper % >14% Vaccine considered safe in adults if T-helper count >200 &/or T-helper % >14% If immune serum globulin prescribed to prevent Hep A, separate injections by at least two weeks If immune serum globulin prescribed to prevent Hep A, separate injections by at least two weeks Role of measuring serum IgG measles antibody Role of measuring serum IgG measles antibody Use of gammaglobulin if inadequate antibody in AIDS, dose suggested is 15 ml IM. IVIG may also be okay. Use of gammaglobulin if inadequate antibody in AIDS, dose suggested is 15 ml IM. IVIG may also be okay.

15. NY/NJ AETC Stuart Haber, MD

16. YELLOW FEVER Mosquito-borne disease in tropical South America and Sub- Saharan Africa Mosquito-borne disease in tropical South America and Sub- Saharan Africa Severity of illness from flu-like illness to severe hepatitis and hemorrhagic fever with a classic biphasic illness Severity of illness from flu-like illness to severe hepatitis and hemorrhagic fever with a classic biphasic illness Fatality rate of severe disease ranges from 20% to 65% Fatality rate of severe disease ranges from 20% to 65% Not known if HIV influences presentation of illness Not known if HIV influences presentation of illness Asymptomatic HIV+ recipients of vaccine without adverse effects Asymptomatic HIV+ recipients of vaccine without adverse effects Lower antibody titers in HIV+ children Lower antibody titers in HIV+ children Consider measurement of antibody titer after vaccination Consider measurement of antibody titer after vaccination Vaccine not recommended in symptomatic HIV-positive adults, certainly not if T-helper count <200. Vaccine not recommended in symptomatic HIV-positive adults, certainly not if T-helper count <200.

17. NY/NJ AETC Stuart Haber, MD GLOBAL DISTRIBUTION OF YELLOW FEVER, 1996

18. NY/NJ AETC Stuart Haber, MD YELLOW FEVER Options to taking vaccine: 1.Avoiding areas of transmission altogether 2.If in an area of potential exposure, meticulously avoiding mosquito bites 3.Vaccine waiver letter-this may not be accepted at border. Need to arrange this with consulate prior to leaving USA 4.Distinguish requirements of country from actual zones of endemicity

19. NY/NJ AETC Stuart Haber, MD HEPATITIS A Vaccine response is lower in HIV+ patients, with dramatically low response rate in patients with <200 cells/mm3(Kemper et al, JID 2003 April 15; 187(8):1327- 31) Vaccine response is lower in HIV+ patients, with dramatically low response rate in patients with <200 cells/mm3(Kemper et al, JID 2003 April 15; 187(8):1327- 31) Know if measurable IgG prior to travel. However, actual protective titer against infection is unknown. Know if measurable IgG prior to travel. However, actual protective titer against infection is unknown. Generally, if less than one month prior to travel, give immune serum globulin with option of starting Hepatitis A vaccine series at same time. There are no current recommendations for an accelerated schedule. Generally, if less than one month prior to travel, give immune serum globulin with option of starting Hepatitis A vaccine series at same time. There are no current recommendations for an accelerated schedule. Dose of immune serum globulin: 0.02 ml/kg body weight IM for trip less than three months. If longer trip, give 0.06 ml/kg IM. Dose of immune serum globulin: 0.02 ml/kg body weight IM for trip less than three months. If longer trip, give 0.06 ml/kg IM. Prolonged viral shedding reported in HIV+ patients with acute Hep A Prolonged viral shedding reported in HIV+ patients with acute Hep A

20. NY/NJ AETC Stuart Haber, MD HEPATITIS B Know immune status prior to travel Know immune status prior to travel Risk to international travelers generally low Risk to international travelers generally low Must warn susceptible patients of sexual risk of acquisition Must warn susceptible patients of sexual risk of acquisition Consider extra doses of vaccine if patient a non-responder (Rey et al Vaccine 2000 Jan 18; 18(13):1161- 5) Consider extra doses of vaccine if patient a non-responder (Rey et al Vaccine 2000 Jan 18; 18(13):1161- 5)

21. NY/NJ AETC Stuart Haber, MD MENINGOCOCCUS Endemic to sub-Sahara Africa during the dry season, occasional epidemics reported elsewhere Endemic to sub-Sahara Africa during the dry season, occasional epidemics reported elsewhere Vaccine required for annual Hajj in Mecca Vaccine required for annual Hajj in Mecca Very scant information on HIV and disease. No mention on efficacy of vaccine in HIV infection Very scant information on HIV and disease. No mention on efficacy of vaccine in HIV infection

22. NY/NJ AETC Stuart Haber, MD JAPANESE ENCEPHALITIS Caused by a flavivirus, transmitted by mosquito Caused by a flavivirus, transmitted by mosquito Endemic to rural areas of SE Asia, varies often with season Endemic to rural areas of SE Asia, varies often with season Most cases are subclinical. Symptomatic disease presents as an acute encephalitis--  seizures, paralysis, coma, death; prolonged recovery in survivors and permanent brain injury in some Most cases are subclinical. Symptomatic disease presents as an acute encephalitis--  seizures, paralysis, coma, death; prolonged recovery in survivors and permanent brain injury in some It is a rare disease of travelers It is a rare disease of travelers Killed vaccine recommended for travelers with prolonged stays in endemic areas Killed vaccine recommended for travelers with prolonged stays in endemic areas Vaccine occasionally causes severe allergic reaction requiring emergent care Vaccine occasionally causes severe allergic reaction requiring emergent care One study demonstrating reduced antibody titers in HIV+ children vaccinated with JE vaccine One study demonstrating reduced antibody titers in HIV+ children vaccinated with JE vaccine Alteration in presentation of illness in HIV-infected people not known Alteration in presentation of illness in HIV-infected people not known

23. NY/NJ AETC Stuart Haber, MD POLIO Most world transmission currently in south Asia and sub-Sahara Africa Most world transmission currently in south Asia and sub-Sahara Africa Only inactivated polio vaccine (IPV) available in the USA Only inactivated polio vaccine (IPV) available in the USA Usually give one adult dose, unless primary series never done or completed Usually give one adult dose, unless primary series never done or completed

24. NY/NJ AETC Stuart Haber, MD OTHER VACCINES Typhoid: two vaccines available: one live and one killed-use only the latter in HIV+ patients. Typhoid: two vaccines available: one live and one killed-use only the latter in HIV+ patients. Typhim Vi has lower antibody response rate in patients with less than 200 CD4+ T lymphs (Vaccine 1999 Aug 6;17(23-24):2941-45) Typhim Vi has lower antibody response rate in patients with less than 200 CD4+ T lymphs (Vaccine 1999 Aug 6;17(23-24):2941-45) Influenza-year-round endemicity in the tropics and April - September in southern hemisphere. No recommendations on revaccinating prior to travel Influenza-year-round endemicity in the tropics and April - September in southern hemisphere. No recommendations on revaccinating prior to travel Diptheria/Tetanus Diptheria/Tetanus Pneumococcus Pneumococcus

25. NY/NJ AETC Stuart Haber, MD PENICILLIUM MARNEFFEI Fungal infection endemic to SE Asia, acquired by inhaling spores Fungal infection endemic to SE Asia, acquired by inhaling spores Opportunistic infection in AIDS Opportunistic infection in AIDS Chronic illness with fever, weight loss, anemia, generalized lymphadenopathy, hepatomegaly, umbilicated papules. Other organ systems can also be involved. Chronic illness with fever, weight loss, anemia, generalized lymphadenopathy, hepatomegaly, umbilicated papules. Other organ systems can also be involved. Diagnosis:bone marrow, skin lesion, blood culture Diagnosis:bone marrow, skin lesion, blood culture Treatment: Ampho B, followed by itraconazole Treatment: Ampho B, followed by itraconazole

26. NY/NJ AETC Stuart Haber, MD

27. VISCERAL LEISHMANIASIS Protozoan parasite transmitted by sandflies Protozoan parasite transmitted by sandflies 90% world cases acquired in India, Bangladesh, Sudan, Nepal, Brazil; and also endemic in Mediterranean countries 90% world cases acquired in India, Bangladesh, Sudan, Nepal, Brazil; and also endemic in Mediterranean countries Typically a chronic illness with prolonged incubation period. Typically have hepatosplenomegaly, fevers, weight loss Typically a chronic illness with prolonged incubation period. Typically have hepatosplenomegaly, fevers, weight loss In AIDS, worse cytopenias, and atypical presentations: pleuropulmonary, GI In AIDS, worse cytopenias, and atypical presentations: pleuropulmonary, GI Serologic tests less sensitive in AIDS Serologic tests less sensitive in AIDS Lower treatment response in AIDS Lower treatment response in AIDS HAART and secondary prophylaxis improves survival HAART and secondary prophylaxis improves survival

28. NY/NJ AETC Stuart Haber, MD TUBERCULOSIS Know PPD status prior to trip Know PPD status prior to trip Repeat PPD after return, especially after prolonged trip. Repeat PPD after return, especially after prolonged trip. Risk of acquisition might be much higher in health care setting Risk of acquisition might be much higher in health care setting

29. NY/NJ AETC Stuart Haber, MD APPROACH TO THE RETURNING HIV-POSITIVE TRAVELER Review dates and itinerary Review dates and itinerary More aggressive evaluation of asymptomatic patient if visit to developing areas was prolonged More aggressive evaluation of asymptomatic patient if visit to developing areas was prolonged For symptomatic patients, check incubation periods for the more common diseases of travelers: For symptomatic patients, check incubation periods for the more common diseases of travelers: Short (less than one week):bacterial diarrhea, Cryptosporidium, hemorrhagic fevers Short (less than one week):bacterial diarrhea, Cryptosporidium, hemorrhagic fevers Medium (up to one month): Giardia, Entamoeba, Malaria, Salmonella typhi, leptospirosis Medium (up to one month): Giardia, Entamoeba, Malaria, Salmonella typhi, leptospirosis Long: Malaria, Visceral leishmaniasis, viral hepatitis, amoebic liver abscess, Schistosomiaisis Long: Malaria, Visceral leishmaniasis, viral hepatitis, amoebic liver abscess, Schistosomiaisis

30. NY/NJ AETC Stuart Haber, MD EOSINOPHILIA May see this anyway in HIV-infected persons May see this anyway in HIV-infected persons However, in setting of travel to indigenous areas, helminthic infections should be looked for in fecal smears However, in setting of travel to indigenous areas, helminthic infections should be looked for in fecal smears

31. NY/NJ AETC Stuart Haber, MD SUMMARY Precautions generally same for HIV and non-HIV infected travelers Precautions generally same for HIV and non-HIV infected travelers Decisions regarding live vaccines are very weighted to patient’s immune status Decisions regarding live vaccines are very weighted to patient’s immune status May anticipate lower response to all vaccines and hence increased risk of disease May anticipate lower response to all vaccines and hence increased risk of disease Incomplete information currently on need for dose or drug changes for malaria prevention in patients taking ritonavir Incomplete information currently on need for dose or drug changes for malaria prevention in patients taking ritonavir Patients taking proper precautions and not severely immunocompromised should do well. Patients taking proper precautions and not severely immunocompromised should do well. Sometimes, travel itinerary should be modified to avoid potential exposures Sometimes, travel itinerary should be modified to avoid potential exposures Differential diagnosis of illness in returning HIV-positive traveler can be very broad both in short term and long term follow-up Differential diagnosis of illness in returning HIV-positive traveler can be very broad both in short term and long term follow-up