1. TRAVEL MEDICINE EVALUATION OF FEVER AND MEDICAL EMERGENCIES IN THE RETURNING TRAVELER

2. Outline of Travel Medicine Issues Evaluation of Fever in the Returning Traveler Evaluation of Fever in the Returning Traveler Medical Emergencies in Travelers Medical Emergencies in Travelers Traveler’s Diarrhea Traveler’s Diarrhea Prevention of Infection: Vaccines and Antibiotic Prophylaxis Prevention of Infection: Vaccines and Antibiotic Prophylaxis Geographic Infections : Abroad and at Home Geographic Infections : Abroad and at Home

3. Overview of Travel Related Illness 20 to 70 % of 50 million travelers to the developing world report illness associated with travel. 20 to 70 % of 50 million travelers to the developing world report illness associated with travel. 1 to 5 % end up seeking medical care 1 to 5 % end up seeking medical care 1 in 100,000 dies of a travel related illness 1 in 100,000 dies of a travel related illness

4. Evaluation of Fever in the Returning Traveler Careful documentation regarding Careful documentation regarding Time of onset of symptoms Time of onset of symptoms Travel locales and accommodations Travel locales and accommodations Activities and exposures Activities and exposures Host factors – medical /immune status Host factors – medical /immune status

5. Evaluation of Fever – Time Factor Timing of exposures –a powerful tool Timing of exposures –a powerful tool Calculation of incubation periods Calculation of incubation periods Duration of total travel- probability of an infection increases with stay ( ie. relative risk of malaria is 80 fold for stays of >6 mos compared to a week) Duration of total travel- probability of an infection increases with stay ( ie. relative risk of malaria is 80 fold for stays of >6 mos compared to a week) Short-term travel rarely leads to helminthic infections; seen more commonly in immigrants Short-term travel rarely leads to helminthic infections; seen more commonly in immigrants Fevers due to infection occurring more than one year after travel is distinctly uncommon. Fevers due to infection occurring more than one year after travel is distinctly uncommon.

6. Incubation Periods Less than 2 weeks Less than 2 weeks Malaria Malaria Ricketsiae Ricketsiae Dengue Dengue Typhoid Typhoid Diarrheal illnesses. Diarrheal illnesses. 6 weeks or more Malaria 6 weeks or more Malaria TB TB Hepatitis B Leishmaniasis Hepatitis B Leishmaniasis Rabies Rabies Two – Six weeks Two – Six weeks Malaria Malaria Hepatitis A, E Hepatitis A, E Leptospirosis Leptospirosis Amebic abscess Schistosomiasis

7. Evaluation of Fever: Prophylaxis History Detailed vaccine/prophylaxis history- Detailed vaccine/prophylaxis history- This does not exclude certain illnesses This does not exclude certain illnesses (ie: efficacy of yellow fever vaccine is greater than typhoid vaccine) (ie: efficacy of yellow fever vaccine is greater than typhoid vaccine) Malarial prophylaxis regimen may fail based on resistance patterns and patient compliance Malarial prophylaxis regimen may fail based on resistance patterns and patient compliance

8. Evaluation of Fever: Exposures Food and Beverage Intake Food and Beverage Intake Arthropod and Animal contacts Arthropod and Animal contacts Recreational Activities- Hiking, Water exposures –fresh and salt water Recreational Activities- Hiking, Water exposures –fresh and salt water Sexual contacts Sexual contacts

9. Evaluation of Fever - Workup Physical exam should carefully focus on: Physical exam should carefully focus on: Skin for lesions, rash, genital lesions Skin for lesions, rash, genital lesions Lymph node, spleen and liver enlargement Lymph node, spleen and liver enlargement Laboratory Tests: Laboratory Tests: CBC with diff., LFT’s, Blood cultures, CXR and malarial smears x 3 CBC with diff., LFT’s, Blood cultures, CXR and malarial smears x 3 Stool studies if symptomatic- O&P, cultures for enteric pathogens (SSCY) Stool studies if symptomatic- O&P, cultures for enteric pathogens (SSCY) Serology if indicated by LFT’s (Hepatitis A,B,E, or E.Histolytica). Serology if indicated by LFT’s (Hepatitis A,B,E, or E.Histolytica).

10. Fever and Eosinophilia Peripheral eosinophilia is associated with helminthic infections that migrate through tissues - rarely with luminal infections Peripheral eosinophilia is associated with helminthic infections that migrate through tissues - rarely with luminal infections Acute Schistosomiasis Acute Schistosomiasis Acute Trichinosis Acute Trichinosis Acute Strongyloides Acute Strongyloides Lymphatic Filariasis Lymphatic Filariasis

11. Evaluation of Fever Emergencies Hemorrhagic Fevers Hemorrhagic Fevers Meningococcus Meningococcus Rickettsiae Rickettsiae Leptospirosis Leptospirosis Plague- Yersinia Plague- Yersinia *Dengue *Dengue Other viral hemorrhagic fevers (Lassa, Rift Valley, Congo-Crimean) Other viral hemorrhagic fevers (Lassa, Rift Valley, Congo-Crimean)

12. Hemorrhagic Fevers: Dengue Fever Endemic in Caribbean, Central and South America and South Asia Endemic in Caribbean, Central and South America and South Asia Estimated 100 million cases/yr, with symptoms ranging from mild fever to shock and death. Estimated 100 million cases/yr, with symptoms ranging from mild fever to shock and death. Four distinct serotype (1-4) of this flavivirus, transmitted by mosquito Four distinct serotype (1-4) of this flavivirus, transmitted by mosquito Prior exposure increases risk of DHF-shock Prior exposure increases risk of DHF-shock

13. Dengue:Clinical Picture Incubation period of 3-10 days Incubation period of 3-10 days Fever, retro-orbital headache, myalgias- arthralgias –”break-bone fever” Fever, retro-orbital headache, myalgias- arthralgias –”break-bone fever” Rash occurs 2- 5 days post fever onset,seen in 50% Rash occurs 2- 5 days post fever onset,seen in 50% GI symptoms in about 50% GI symptoms in about 50% Thrombocytopenia, leukopenia - 16-55% Thrombocytopenia, leukopenia - 16-55% Hemorrhagic Fever- seen with vascular leak and shock state Hemorrhagic Fever- seen with vascular leak and shock state Serologic studies Serologic studies Treatment is supportive only Treatment is supportive only

14. Evaluation of Fever Emergencies Fever and Confusion and lethargy Fever and Confusion and lethargy P.falciparum malaria (cerebral form) P.falciparum malaria (cerebral form) N.meningococcus N.meningococcus Rickettsiae – R. conori, proweseki Rickettsiae – R. conori, proweseki

15. Malaria Fever in traveler from malarial region Fever in traveler from malarial region Highest after rainy season; uncommon at altitude >2000 ft Highest after rainy season; uncommon at altitude >2000 ft Over 1,500 cases in US /yr Over 1,500 cases in US /yr Appropriate prophylaxis is about 80% effective. Appropriate prophylaxis is about 80% effective. Incubation period varies by species- Incubation period varies by species- P.falciparum- 12-14 d P. vivax/ovale -up to 2 mos, can be years P. vivax/ovale -up to 2 mos, can be years P.malariae- 35 days P.malariae- 35 days *P. knowlesi- transmitted in SE Asia; endemic in monkeys *P. knowlesi- transmitted in SE Asia; endemic in monkeys

16. Malaria:Evaluation and Rx Fever associated with sweats, headache, myalgias. Fever associated with sweats, headache, myalgias. Anemia, thrombocytopenia Anemia, thrombocytopenia Thick smears q 6-12 hours for 48 hrs. First smear + in 95%. Thick smears q 6-12 hours for 48 hrs. First smear + in 95%. Parasitemia of greater than 3% should be hospitalized; greater than 5% have significant mortality when treated. Parasitemia of greater than 3% should be hospitalized; greater than 5% have significant mortality when treated.

17. Malaria:Treatment For Chloroquine-sensitive species (P.vivax/ovale/malariae): For Chloroquine-sensitive species (P.vivax/ovale/malariae): Chloroquine 600mg, followed by 300mg at 6, 24, 48 hrs.Chloroquine 600mg, followed by 300mg at 6, 24, 48 hrs. For Chloroquine-Resistant P.falciparum Quinine+Doxycycline -7 days Quinine+Doxycycline -7 days Malarone – 3 days (if no malarone prophylaxis) Malarone – 3 days (if no malarone prophylaxis) Mefloquine – 1250 mg in divided doses Mefloquine – 1250 mg in divided doses

18. Evaluation of Fever Emergencies Respiratory Distress Respiratory Distress Malaria Malaria Hanta virus Hanta virus Influenza Influenza SARS SARS Avian Influenza. Avian Influenza.

19. Travelers’ Diarrhea Travel to the developing world carries a 40-60% risk of diarrhea- usually benign and self-limited. Travel to the developing world carries a 40-60% risk of diarrhea- usually benign and self-limited. More than 90% is bacterial, and food/water borne. More than 90% is bacterial, and food/water borne. Most common pathogen – Enterotoxin E.coli (ETEC). Most common pathogen – Enterotoxin E.coli (ETEC). Parasitic enteritis requires a more contaminated environment than usually encountered by tourists. Parasitic enteritis requires a more contaminated environment than usually encountered by tourists. Note: Airline food is prepared in departure city. Note: Airline food is prepared in departure city.

20. Travelers’ Diarrhea- Risk Factors Low Risk (<10%) – N.Europe,Australia, US, Canada-but note high Giardia risk in US West/NE mountains Low Risk (<10%) – N.Europe,Australia, US, Canada-but note high Giardia risk in US West/NE mountains Moderate Risk (up to 20%) – Caribbean, Mediterranean, and Israel Moderate Risk (up to 20%) – Caribbean, Mediterranean, and Israel High Risk (>30%) – Asia, Africa, Mexico, Central and South America High Risk (>30%) – Asia, Africa, Mexico, Central and South America Gastric bypass and resection, histamine blockers will allow bacteria to survive to small bowel. Gastric bypass and resection, histamine blockers will allow bacteria to survive to small bowel.

21. Travelers’ Diarrhea: Clues to Pathogens Watery and Afebrile Watery and Afebrile Most common pathogen is ETEC- the prototype travelers’ diarrhea is self limited Most common pathogen is ETEC- the prototype travelers’ diarrhea is self limited  Bloody Diarrhea with Fever Salmonella, Shigella, Campylobacter and Yersina are invasive; E.histolytica. Salmonella, Shigella, Campylobacter and Yersina are invasive; E.histolytica.  Vibrio cholerae will cause a profound secretory diarrhea (“rice water”), with highest risk of dehydration/death.

22. Travelers’ Diarrhea: Therapy Prevention: prophylactic antibiotics are not recommended unless a person’s medical condition or dehydration risk is severe- Prevention: prophylactic antibiotics are not recommended unless a person’s medical condition or dehydration risk is severe- IBD Renal Immunosuppresion AIDS IBD Renal Immunosuppresion AIDS  Empiric Abx- quinolones; for convenience, consider qd dosing with levofloxacin indicated in cases of fever, blood or pus, and > 4 daily stools.

23. Skin Lesions in Travelers Arthopod Bites- Arthopod Bites- Myiasis -botfly larvae will penetrate skin and mature leading to a nodule. Myiasis -botfly larvae will penetrate skin and mature leading to a nodule. Tungiasis (sand flea larvae are expelled under skin after a blood meal). Tungiasis (sand flea larvae are expelled under skin after a blood meal). Rickestiae will see a necrotic ulcer Rickestiae will see a necrotic ulcer

24. Skin Lesions in Travelers Skin Ulcers Skin Ulcers Tularemia Tularemia Atypical Mycobacterial Atypical Mycobacterial Endemic fungal Endemic fungal STD’s –genital ulcers- Syphilis, LGV,Chanchroid STD’s –genital ulcers- Syphilis, LGV,Chanchroid Creeping Eruptions Creeping Eruptions Cutaneous larva migrans (hookworm larva) Cutaneous larva migrans (hookworm larva) Loiasis Loiasis Strongyloidiasis. Strongyloidiasis.

26. Cutaneous Leishmaniasis

27. Preventable Traveler’s Infections Yellow Fever – viral, mosquito-borne,lethal Yellow Fever – viral, mosquito-borne,lethal Malaria – parasitic, mosquito-borne, lethal Malaria – parasitic, mosquito-borne, lethal Typhoid Fever –bacterial, food- borne,contagious Typhoid Fever –bacterial, food- borne,contagious Hepatitis A – viral, food-borne, contagious Hepatitis A – viral, food-borne, contagious Meningococcus – bacterial, contagious, lethal, seasonal and epidemic. Meningococcus – bacterial, contagious, lethal, seasonal and epidemic. Japanese Encephalitis- viral, mosquito-borne, seasonal, lethal, low-risk for short-term travelers Japanese Encephalitis- viral, mosquito-borne, seasonal, lethal, low-risk for short-term travelers

28. Yellow Fever Prevention An Equatorial infection in both East/West An Equatorial infection in both East/West A live-virus vaccine A live-virus vaccine Only vaccination legally required by certain countries for entry. Only vaccination legally required by certain countries for entry. Four reported cases of vaccine-related multi- organ failure, with three deaths in 1996-98 in USA. Four reported cases of vaccine-related multi- organ failure, with three deaths in 1996-98 in USA. Contraindicated for pregnant and immunodeficient persons (live-virus). Contraindicated for pregnant and immunodeficient persons (live-virus). Single IM dose; booster every ten years Single IM dose; booster every ten years

31. Malaria Prevention Nearly 300 million cases worldwide each year, with more than one million deaths. Nearly 300 million cases worldwide each year, with more than one million deaths. Four species: Plasmodium falciparum, vivax, ovale and malariae. Fatalities with falciparum. Four species: Plasmodium falciparum, vivax, ovale and malariae. Fatalities with falciparum. Several hundred cases/year in US travelers. During 1980-93, 3005 US cases with 51 deaths (1.7%). Several hundred cases/year in US travelers. During 1980-93, 3005 US cases with 51 deaths (1.7%). Highest risk occurs in Sub-Saharan Africa. Highest risk occurs in Sub-Saharan Africa. Need to consider up-to-date resistance patterns. Need to consider up-to-date resistance patterns.

32. Malarial Prevention Prophylactic antibiotics are 90-95% effective. Prophylactic antibiotics are 90-95% effective. Regimens routinely require starting pills 1-2 weeks prior to, and for 4 weeks following exposure. Regimens routinely require starting pills 1-2 weeks prior to, and for 4 weeks following exposure. Chloroquine is the first-line agent for travel to areas that still have chloroquine-sensitive P.falciparum, restricted to Central America, Middle East. Chloroquine is the first-line agent for travel to areas that still have chloroquine-sensitive P.falciparum, restricted to Central America, Middle East. Chloroquine resistant strains of P.vivax have now appeared in Africa and Asia Chloroquine resistant strains of P.vivax have now appeared in Africa and Asia

34. Malaria Prevention Topical insect repellants which include (DEET). Can see dermatitis, and neurotoxicity from absorption (caution with children-use lower %) Topical insect repellants which include (DEET). Can see dermatitis, and neurotoxicity from absorption (caution with children-use lower %) Mosquito netting sprayed with permethrin. Mosquito netting sprayed with permethrin. Note: Yellow Fever is transmitted by mosquitos that bite during daytime, malaria transmitted at night. Note: Yellow Fever is transmitted by mosquitos that bite during daytime, malaria transmitted at night. PREGNANCY- Chloroquine is safe, Mefloquine appears safe, Malarone data is still insufficient. PREGNANCY- Chloroquine is safe, Mefloquine appears safe, Malarone data is still insufficient.

35. Malaria Prevention for Travel to Chloroquine Resistant (CR)Regions Mefloquine- 250 mg q week (-1 to 4+ travel) active against all species, yet resistant strains of P.falciparum now exist in Africa and in Thai- Cambodian-Myanmar regions. Side effects include neuropsychiatric and GI. Mefloquine- 250 mg q week (-1 to 4+ travel) active against all species, yet resistant strains of P.falciparum now exist in Africa and in Thai- Cambodian-Myanmar regions. Side effects include neuropsychiatric and GI. Malarone – combination of atovaquone/proguanil. Taken qd 1-2 days prior to,during, and one week post. Equivalent to mefloquine vs. CR P.falciparum. Malarone – combination of atovaquone/proguanil. Taken qd 1-2 days prior to,during, and one week post. Equivalent to mefloquine vs. CR P.falciparum. Doxycycline- 100 mg qd 1-2 days prior, 4 wks. post travel. Issue of photosensitivity. Doxycycline- 100 mg qd 1-2 days prior, 4 wks. post travel. Issue of photosensitivity.

36. Typhoid Fever and Prevention Salmonella typhi is still prevalent in Asia, Africa and Latin America. Salmonella typhi is still prevalent in Asia, Africa and Latin America. Risk appears greatest in Indian subcontinent. Risk appears greatest in Indian subcontinent. Vaccination is best advised for those going to more remote regions, or during reported outbreaks Vaccination is best advised for those going to more remote regions, or during reported outbreaks Oral vaccine(Vivotif)- taken prior to travel qod x 4, and can be boosted every 5 years. Oral vaccine(Vivotif)- taken prior to travel qod x 4, and can be boosted every 5 years. Injectable(Typhim)- provides protection for 1- 2 yrs Injectable(Typhim)- provides protection for 1- 2 yrs Both vaccinations provide about 50-80% protection Both vaccinations provide about 50-80% protection

39. Homeland Security - Travel Medicine in the USA Endemic infections must be considered in evaluation of fever after US travel. Endemic infections must be considered in evaluation of fever after US travel. Recreational activities increase the chance of exposure to arthropods and the endemic fungi Recreational activities increase the chance of exposure to arthropods and the endemic fungi Ticks – Babesios (New England coast/islands) Ticks – Babesios (New England coast/islands) Lyme (Northeast coast, WI,CA) Lyme (Northeast coast, WI,CA) RMSF (Appalachia, Northeast) RMSF (Appalachia, Northeast) Erhlichiosis (Northeast, MO, AR) Erhlichiosis (Northeast, MO, AR) Tick Paralysis ( Rocky Mts.) Tick Paralysis ( Rocky Mts.)

40. US Travel Medicine Endemic Mycoses – Pulmonary/Systemic Endemic Mycoses – Pulmonary/Systemic Blastomycosis – LA, WI, Miss. River valley Blastomycosis – LA, WI, Miss. River valley Histoplasmosis – Ohio, St.Lawrence and Histoplasmosis – Ohio, St.Lawrence and Mississippi river valleys Mississippi river valleys Coccidiomycosis - desert SW, San Joaquin Coccidiomycosis - desert SW, San Joaquin  Hanta Virus Pulmonary Syndrome- NM,CO,AZ  Plague- flea bite, AZ bubonic not pneumonic

41. Prevention of Infections Related to Travel – Abroad and At Home Potential exposures should signal a series of immunizations and prophylaxis. Potential exposures should signal a series of immunizations and prophylaxis. Resources: Resources: WWW. ISTM.org. WWW. ISTM.org. WWW. Cdc.gov WWW. Cdc.gov WWW. Tropnet.net WWW. Tropnet.net Travel Medicine Clinics Travel Medicine Clinics

42. BON VOYAGE Be Careful Out There