EMPORIATRIC MEDICINE AND THE HIV-INFECTED TRAVELER

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

2. 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 • Get list of medical clinics from IAMAT www.iamat.org • 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 • Be cautious of motor vehicle travel • Swim only in chlorinated water • Health insurance: both international insurance(try credit card companies, yellow pages, internet) and air ambulance insurance: www.airambulancedirectory.com NY/NJ AETC Stuart Haber, MD

3. SPECIFIC PRECAUTIONS FOR ENTERITIS • Developingcountries: especially important in patients with severe immunosuppression • 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!! • No tap water, ice cubes. Bottled water, including for brushing teeth! • Portable water purifiers ( with absolute one micron filter) NY/NJ AETC Stuart Haber, MD

4. TRAVELER’S DIARRHEA • 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 • 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 • Treatment for uncomplicated disease:cipro 500mg BID for three to seven days with first day imodium. NY/NJ AETC Stuart Haber, MD

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

6. INTERNATIONAL SCREENING OF TRAVELERS FOR HIV INFECTION • Primarily aimed for those with extended stays: work visas, students • Approximately 50 countries may block entry of HIV+ travelers • Check with consular office(s) or go to 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. NY/NJ AETC Stuart Haber, MD

7. TIMING OF HAART ACROSS TIME ZONES • Take more doses in the period than less. • East to West: extra dose of Nukes, viramune and PIs at bedtime • West to East: extra dose next morning • Efavirenz doesn’t need an extra dose (G. Moyle, personal comm.) • 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 NY/NJ AETC Stuart Haber, MD

8. DRUG AND MEDICAL CARE ISSUES • 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 • Avoid if possible, new medication changes just prior to travel NY/NJ AETC Stuart Haber, MD

9. MALARIA PREVENTION • Same precautions and prophylaxis with all travelers • Review itinerary on www.cdc.gov malaria site • 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 • 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, 7th 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) • 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) NY/NJ AETC Stuart Haber, MD

10. 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) • Treat non-severe malaria with malarone 4 pills/day for three days, or with lariam (increased risk of seizures). • Self-treatment not generally advised NY/NJ AETC Stuart Haber, MD

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

12. VACCINES • In most developing areas of world, following vaccine-preventable illnesses are addressed: • Measles • Hepatitis A • Typhoid Fever • Influenza • Yellow fever • Hepatitis B • Polio • Japanese encephalitis • Rabies • Cholera • Meningococcus NY/NJ AETC Stuart Haber, MD

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

14. MEASLES VACCINE • 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. • 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% • If immune serum globulin prescribed to prevent Hep A, separate injections by at least two weeks • 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. NY/NJ AETC Stuart Haber, MD

15. NY/NJ AETC Stuart Haber, MD

16. YELLOW FEVER • 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 • Fatality rate of severe disease ranges from 20% to 65% • Not known if HIV influences presentation of illness • Asymptomatic HIV+ recipients of vaccine without adverse effects • Lower antibody titers in HIV+ children • Consider measurement of antibody titer after vaccination • Vaccine not recommended in symptomatic HIV-positive adults, certainly not if T-helper count <200. NY/NJ AETC Stuart Haber, MD

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

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

19. 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) • 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. • 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 NY/NJ AETC Stuart Haber, MD

20. HEPATITIS B • Know immune status prior to travel • Risk to international travelers generally low • 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) NY/NJ AETC Stuart Haber, MD

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

22. JAPANESE ENCEPHALITIS • Caused by a flavivirus, transmitted by mosquito • 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 • It is a rare disease of travelers • Killed vaccine recommended for travelers with prolonged stays in endemic areas • Vaccine occasionally causes severe allergic reaction requiring emergent care • One study demonstrating reduced antibody titers in HIV+ children vaccinated with JE vaccine • Alteration in presentation of illness in HIV-infected people not known NY/NJ AETC Stuart Haber, MD

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

24. OTHER VACCINES • 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) • Influenza-year-round endemicity in the tropics and April - September in southern hemisphere. No recommendations on revaccinating prior to travel • Diptheria/Tetanus • Pneumococcus NY/NJ AETC Stuart Haber, MD

25. PENICILLIUM MARNEFFEI • Fungal infection endemic to SE Asia, acquired by inhaling spores • Opportunistic infection in AIDS • 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 • Treatment: Ampho B, followed by itraconazole NY/NJ AETC Stuart Haber, MD

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27. VISCERAL LEISHMANIASIS • Protozoan parasite transmitted by sandflies • 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 • In AIDS, worse cytopenias, and atypical presentations: pleuropulmonary, GI • Serologic tests less sensitive in AIDS • Lower treatment response in AIDS • HAART and secondary prophylaxis improves survival NY/NJ AETC Stuart Haber, MD

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

29. APPROACH TO THE RETURNINGHIV-POSITIVE TRAVELER • Review dates and itinerary • 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: • Short (less than one week):bacterial diarrhea, Cryptosporidium, hemorrhagic fevers • Medium (up to one month): Giardia, Entamoeba, Malaria, Salmonella typhi, leptospirosis • Long: Malaria, Visceral leishmaniasis, viral hepatitis, amoebic liver abscess, Schistosomiaisis NY/NJ AETC Stuart Haber, MD

30. EOSINOPHILIA • 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 NY/NJ AETC Stuart Haber, MD

31. SUMMARY • Precautions generally same for HIV and non-HIV infected travelers • 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 • 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. • 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 NY/NJ AETC Stuart Haber, MD