Imported Diseases and Infectious Disease Surveillance

1. Imported Diseases and Infectious Disease Surveillance George Turabelidze, MD, PhD Missouri Department of Health and Senior Services

2. International Tourism • Popularity of international tourism continues to grow • Growth of travel to developing countries exceeds travel growth to developed world • A list of exotic destinations and extreme travel activities is also growing • Exposure to diseases rare in the developed countries is rising

3. World Tourism, 2005 • International tourist arrivals in 2005 hit all-time record of 800 million • The 2005 results represent a 5.5% increase worldwide; higher than the long-term average annual growth rate of 4.1% • Tourism to Asia/Pacific, Middle East, and Africa expected to grow at higher rate compared to average worldwide growth rate • International arrivals are forecasted to reach 1.6 billion by year 2020 UN World Tourism Organization, 2006

4. Africa – 9% Asia/Pacific – 8% Middle East – 8% Americas – 6% Europe – 4% Only region without increase in international arrivals in the last 5 years was North America (-.3%) Travel Increase by Region, 2005 UN World Tourism Organization, 2006

7. Risk of Illness in Travelers • From 22 to 64% of travelers to the developing world report some kind of health problem(Steffen et al., 2003) • Up to 8% of all American travelers to developing world seek medical care; each day of travel carries 3-4% risk of illness(Hill, 2000) • About 26%-27% of febrile travelers will needhospitalization(Wilson et al.2007, Bottieau et al., 2006)

8. Risk of Illness in Travelers • According to US Department of Commerce, about 12 million US residents, or 4% of total US population, traveled to the developing world in 2006 • About 220,000 Missourians could have been travelers to the developing world in 2006 • An estimated 17,000 Missourians would seek medical care after the travel

9. Extreme Travel • Defined as travel to remote destinations or participating in unusual high-risk activities during travel • The average age of adventure traveler is 32 years (44 years for the American traveler as a whole) • The risk of illness increases with longer duration and more remote travel

11. Surveillance of Imported Diseases • Detection of sentinel events in travelers can lead to outbreak detection • Travelers serve as surveillance tool for imported diseases • Travelers could be a warning sign for disease outbreaks in developing countries • Cluster of infections in returning travelers could warn of specific risk to new travelers to that destination(s) and increase their protection

12. Imported Diseases Surveillance Networks • GeoSentinel – clinical surveillance data on travelers from six continents • TropNetEurop – clinician-basedEuropean Network on Imported Infectious Disease Surveillance • DoD GEIS – syndromic surveillance by US DoD Global Emerging Infections System • Quarantine Activity Reporting System (QARS), a web-based secure electronic system • Public Health departments surveillance

13. Quarantine Stations • 18 U.S. Quarantine Stations (QS) based at major ports of entry and land border crossings in 2006 • Foreign Quarantine Regulations (Title 42 CFR Part 71) • Required reportable syndromes by conveyance operators entering U.S. ports: • Fever ≥ 100°F (37.8°C) > 48 hours • Fever + rash • Fever + glandular swelling • Fever + jaundice • Diarrhea (≥ 3 or more loose stools in a 24 hour period) • Recommended reportable syndromes by conveyance operators entering U.S. • Fever + abnormal bleeding • Fever + cough or difficulty breathing • Fever + head or neck pain

14. Final Diagnoses of Deaths and Illnesses Reported in QARS During and After Travel, 2006 Kornylo, et al., CDC, CSTE Presentation, 2007

15. Fever After Stay in the Tropics • 1743 febrile patients were prospectively followed at the Institute of Tropical Medicine in Antwerp, Belgium (Bottieau et al.,2006) • Tropical diseases –39%, cosmopolitan –34%, and unknown –24% • Africa – malaria (35%), rickettsiosis (4%) Asia– dengue (12%), malaria (9%), enteric fever – (4%) Latin America– dengue (8%), malaria (4%)

16. Fever in Returned Travelers • 6957febrile travelers (GeoSentinel, 1997-2006 data) • 35% with systemic febrile illness, 22% unspecified fever,15% diarrhea, 14% respiratory, and 10% other diagnosis • Malaria most common, followed by dengue, enteric fever, rickettsiosis • Malaria overwhelmingly more common in visitors to Pacific Islands and sub-Saharan Africa • Enteric fever common in south-central Asia travelers, whereas rickettsioses in southern Africa travelers Wilson et al, 2007

17. Travel-Related Hospitalization • Most common diagnoses in 211 travelers hospitalized in 1999-2003 in Israel: malaria (26%), unspecified fever (16%), dengue (13%), diarrhea (11%), leishmaniasis (9%) • Most common by destination: Africa - malaria, FUO, diarrhea Asia - dengue, FUO, diarrhea Latin America - leishmaniasis, malaria, FUO Stienlauf, et al.,2005

18. Imported Diseases in Relation to Traveler’s Place of Exposure • GeoSentinel’s clinical data (30 sites) on 17,353 ill travelers returning from six developing regions, 1996-2004 • 67% of all travelers with four syndromes: fever, acute diarrhea, rash, chronic diarrhea • Malaria, dengue, mononucleosis, rickettsiosis, typhoid fever most common in fever patients • Travel destinations were associated with the probability of certain diseases Freedman et al., 2006

19. Freedman et al., 2006

20. Imported Diseases in Relation to Traveler’s Place of Exposure • Fever: sub-Saharan Africa, southeast Asia • Acute diarrhea: south central Asia • Rash: Caribbean, Central/South America • Parasite-induced diarrhea more common than bacterial in all regions except southeast Asia • Rickettsiosis more common than typhoid or dengue in sub-Saharan travelers Freedman et al., 2006

21. Specific Diagnoses within Selected Syndromes • Fever:malaria, dengue, EBV, rickettsiosis, typhoid fever • Acute diarrhea: parasitic (giardiasis, amebiasis), bacterial (campylobacter, shigella, salmonella) • Rash:insect bite, cutaneous larva migrans, allergic rash, skin abscess, mycosis, leishmaniasis, myiasis, swimmer’s itch, impetigo, scabies Modified from Freedman et al., 2006

22. Top Etiologic Diagnoses by Region • Carribean:cutaneous larva migrans, dengue, insect bite, giardiasis, strongyloidosis, amebiasis • Central America:insect bite, cutaneous larva migrans, amebiasis, strongyloidosis, giardiasis, malaria, dengue, myasis • South America:giardiasis, insect bite, amebiasis, leishmaniasis, dengue, malaria cutaneous larva, strongyloidosis, myasis, campylobacter

23. Top Etiologic Diagnoses by Regions • Africa:malaria, insect bite, giardiasis, strongyloidosis, amebiasis, skin abscess • South Asia:giardiasis, insect bite, dengue, skin abscess, malaria, enteric fever, amebiasis, campylobacter • Southeast Asia: dengue, campylobacter, insect bite, cutaneous larva, malaria, skin abscess, giardiasis • Other regions: malaria, insect bite, amebiasis, giardiasis, skin abscess

24. Most Common Tropical Infections by Time Interval Between Return Date and Fever Onset • < 1 month:falciparum malaria, rickettsiosis, dengue, non-falciparum malaria, acute schistosomiasis, enteric fever • 1-3 months:non-falciparum malaria, falciparum malaria, acute schistosomiasis, helminthic eneteritis • 4-12 months:non-falciparum malaria, falciparum malaria, protozoan enteritis • Data from 1962 tropical travelers seen in outpatient and inpatient settings in Antwerp, Belgium from 2000 to 2005 (Bottieau et al., 2007)

25. Relative Risk for Travelers • High: viral diarrhea, E.coli enteritis, URI • Moderate:malaria (w/o prophylaxis), salmonella, shigella, campylobacter, giardiasis, amebiasis, hepatitis A, dengue, EBV, gonorrhea, chlamydia, herpes simplex • Low:malaria (with prophylaxis), leptospirosis, typhoid, cholera, HIV, HBV, syphilis, Lyme, schistosomiasis, TB, helminthosis, ricckettsiosis, borelliosis, measles • Very low:anthrax, plague, VHF, tularemia, melioidosis, legionella, yellow fever, rabies, poliomyelitis, diphtheria, trypanosomiasis, trichinosis,, filariasis, toxocariasis, echinococcosis, gnathostomiasis Adapted from Spira, 2003

27. Approaching Public Health Report of Traveler with Illness • Person (demographics, vaccinations, chemoprophylaxis) • Place (travel region, exposures) • Time (travel dates, exposure dates, incubation period)

28. Immunizations for Travelers • Routine vaccinations • Required:Yellow fever, meningococcal (Saudi Arabia) • Recommended:Hepatitis A and B, japanese encephalitis, meningococcal, rabies, tick-borne, encephalitis, typhoid, varicella

29. Chemoprophylaxis for Travelers • Malaria (doxycycline, mefloquine, cloroquine, primaquine, etc.) • Traveler’s diarrhea (rifaximin, ciprofloxacin, azithromycin) • Leptospirosis (doxycycline) • Rickettsiosis (doxycycline)

30. Exposure-based Risk Factors,Ingestion • Untreated water – hepatitis A/E, salmonella, shigella, giardia, poliomyelitis, amoebiasis, cryptosporidium, cyclospora, dracunculiasis, cholera, typhoid fever • Unpasteurized dairy – brucellosis, salmonellosis, Q fever, shigella, listeriosis • Undercooked food – salmonellosis, shigella, E.coli, campylobacter, trichinosis, helminthosis, amoebiasis, toxoplasma

31. Exposure-based Risk Factors,Insect Exposure • Mosquitoes – malaria, dengue, yellow fever, encephalitis, filariasis • Lice – epidemic typhus, relapsing fever, trench fever • Fleas – plague, murine typhus • Ticks – Lyme disease, babesiosis, ehrlichiosis, rickettsiosis, encephalitis, Q fever, tularemia, Crimean-Congo hemorrhagic fever • Mites – scrub typhus, scabies • Sandflies – leishmaniasis, bartonellosis, filariasis • Flies, tsetse – trypanosomiasis, onchocerciasis

32. Exposure-based Risk Factors,Animal Contact • Animal mammal contact – anthrax, rabies, Q fever, typhus, tularemia, brucellosis, leptospirosis, echinococcosis • Contact with/aerosolization of rodent urine – Lassa fever, hantavirus, leptospirosis • Exposure to birthing products – Q fever, brucellosis • Exposure to animal hides - anthrax

33. Exposure-based Risk Factors, Recreation • Freshwater exposure –leptospirosis, schistosomiasis, melioidosis, acanthamoeba, naegleria • Soil exposure or ingestion – anthrax, helminthosis, cutaneous larva migrans, melioidosis • Sexual contact – HIV, hepatitis B/C, syphilis, gonorrhea, herpes • Airborne – influenza, measles, tuberculosis • IDU/Transfusions – HIV, hepatitis B and C, malaria, toxoplasmosis, babesiosis • Ill contacts– TB, EBV, meningitis, Lassa, pneumonia

34. Extreme Traveler’s Risk by Exposure • Salt water exposure: skin infection with M.marinum, Aeromonas, V.vulnificus • Freshwater exposure (including white water rafting): leptospirosis, schistosomiasis • Remote trekking: traveler’s diarrhea, rickettsiosis, rabies • Spelunking (caving): histoplasmosis, rabies • Cycling: rabies

35. Arboviral infections Anthrax Dengue Enteric bacterial Enteric viral Fungal respiratory Hantavirus Influenza Legionellosis Measles Meningococcal Plague Pneumonia Q fever Rickettsioses SARS Tularemia Viral hemorrhagic fever Incubation Periods of Travel –Associated Infectious Diseases, Short (< 10 days)

36. Acute HIV American trypanosomiasis Babesiosis Brucellosis Enteric protozoa Q fever Leptospirosis Lyme disease Malaria Measles Rickettsiosis Typhoid fever Viral hemorrhagic fever Incubation Periods of Travel –Associated Infectious Diseases, Medium (10-21 days)

37. African trypanosomiasis Amebiasis Brucellosis Hepatitis A, B, and E Helminthosis Enteric protozoa Filariasis Rabies Malaria Schistosomiasis Typhoid fever Tuberculosis Incubation Periods of Travel –Associated Infectious Diseases, Long (>21 days)

38. Amebiasis Brucellosis HIV Leishmaniasis Malaria Melioidosis Rabies Schistosomiasis Tuberculosis Incubation Periods of Travel –Associated Infectious Diseases, Variable (weeks-years)

40. Malaria • Malaria is among top three causes of fever in travelers to every region in the developing world • Incidence in the United States is about 1200 cases per year; 63 episodes of introduced malaria were detected from 1957 to 2003 • In most severe cases presentation could be similar to hemorrhagic fever illness, such as caused by Ebola virus • Diagnosis of malaria is ruled out only after sequential blood smear testing!

44. Dengue • Caused by flavivirus transmitted by urban mosquito • 329 confirmed cases in US travelers in 1996-2005 • Four serotypes of virus; immunity to one serotype is not cross-protective • Infection ranges from subclinical form to influenza-like to severe with bleeding and shock • Previous dengue infection increases risk of dengue hemorrhagic fever with subsequent infection • Anti-dengue antibodies cross-react with anti-WNV,-yellow fever, -JE, -other flavivirus antibodies

46. Rickettsioses in Travelers • Tick-borne rickettsiosis should be suspected in febrile travelers, especially if rash is present • Vast majority of travelers with rickettsiosis have African tick bite fever (R.africae) or Mediterranean spotted fever (R.conorii) • In 530 German travelers with fever who traveled to southern Africa, 11% had serological evidence of recent rickettsial infection(Jelinek T, Loscher T, 2001) • In Swedish travelers to southern Africa, risk of rickettsiosis was 4 to 5 times higher than risk of malaria(Raeber PA, et al., 2003)

47. Western blot of pooled mouse antisera to R.africae – human isolate (lane 1), R.africae – tick isolate (lanes 2–4), R.conorii – Kenyan strain (lane 5), R.conorii – Moroccan strain (lane 6) and Israeli SFG rickettsia (lane 7).