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


International Tourism: 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


World Tourism, 2005: 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


Travel Increase by Region, 2005: Travel Increase by Region, 2005 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%) UN World Tourism Organization, 2006


Risk of Illness in Travelers: 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 need hospitalization (Wilson et al.2007, Bottieau et al., 2006)


Risk of Illness in Travelers: 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


Extreme Travel: 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


Surveillance of Imported Diseases: 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


Imported Diseases Surveillance Networks: Imported Diseases Surveillance Networks GeoSentinel – clinical surveillance data on travelers from six continents TropNetEurop – clinician-based European 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


Slide13: 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 Quarantine Stations


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


Fever After Stay in the Tropics: 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%)


Fever in Returned Travelers: Fever in Returned Travelers 6957 febrile 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


Travel-Related Hospitalization: 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


Imported Diseases in Relation to Traveler’s Place of Exposure: 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


Slide19: Freedman et al., 2006


Imported Diseases in Relation to Traveler’s Place of Exposure: 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


Specific Diagnoses within Selected Syndromes: 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


Top Etiologic Diagnoses by Region: 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


Top Etiologic Diagnoses by Regions: 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


Most Common Tropical Infections by Time Interval Between Return Date and Fever Onset: 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)


Relative Risk for Travelers: 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


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


Immunizations for Travelers: 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


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


Exposure-based Risk Factors,Ingestion: 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


Exposure-based Risk Factors,Insect Exposure: 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


Exposure-based Risk Factors,Animal Contact: 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


Exposure-based Risk Factors, Recreation: 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


Extreme Traveler’s Risk by Exposure: 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


Incubation Periods of Travel –Associated Infectious Diseases, Short (< 10 days): Incubation Periods of Travel –Associated Infectious Diseases, Short (< 10 days) 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, Medium (10-21 days): Incubation Periods of Travel –Associated Infectious Diseases, Medium (10-21 days) 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, Long (>21 days): Incubation Periods of Travel –Associated Infectious Diseases, Long (>21 days) 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, Variable (weeks-years): Incubation Periods of Travel –Associated Infectious Diseases, Variable (weeks-years) Amebiasis Brucellosis HIV Leishmaniasis Malaria Melioidosis Rabies Schistosomiasis Tuberculosis


Malaria: 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!


Dengue: 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


Rickettsioses in Travelers: 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)


Slide47: 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).


Report of Febrile Illness: Report of Febrile Illness A 29 year old man from Columbia, MO was admitted to a local hospital with a one-day history of fever 104°F, headache, nausea, and vomiting. Two days prior to admission he flew from New York City to St. Louis on commercial airline. According to the patient, one of the passengers who was sitting a few rows behind him was “coughing a lot,” and the patient was convinced that he became infected on the plane. The patient also suspected that the “coughing passenger” was traveling from abroad and that he was probably “spreading unusual disease”. The patient and his family requested a public health investigation and wanted to pursue legal action against the airline for letting an “infectious passenger” on board of the aircraft.


Cabin Airflow Patterns: Cabin Airflow Patterns World Health Organization, 2006 Sterile air entering Heating/cooling HEPA filters High airflow rates Laminar airflow Frequent exchanges


Infections Transmitted on Commercial Airlines (number of reports): Infections Transmitted on Commercial Airlines (number of reports) Food-borne Cholera – 3 Salmonellosis – 15 Staphylococcal – 8 Shigellosis – 3 Viral enteritis – 1 Vector-borne Malaria – 7 Dengue – 1 Airborne/fomites Influenza – 2 Measles – 3 Meningococcal – 0 SARS – 4 Smallpox – 1 Tuberculosis - 2


Cabin Air Quality: Cabin Air Quality No scientific evidence currently exists that links cabin air quality to heightened health risks compared with other modes of transport or with office buildings Existing data suggests that risk of transmission for airborne infections on the aircraft is associated with sitting within two rows of a contagious passenger for a flight time of more than 8 hours


Slide55: ILL TRAVELLERS ASSESSMENT ALGORITHM Travel Destinations Diarrhea, Acute Rash Diarrhea, Chron Fever, Systemic Rash Diarrhea, Acute Fever, Systemic Diarrhea, Chron Fever, Systemic Rash/Diarrhea Acute Diarrhea, Chron Diarrhea, Acute Fever, Systemic Rash/Diarrhea, Chronic Rash Diarrhea, Acute Fever, Systemic Diarrhea, Chron Fever, Systemic Diarrhea, Acute Rash Diarrhea, Acute Diarrhea, Chron Fever Rash/GI Illness America Central America South Asia Southeast Asia South Central Caribbean Africa Sub-Saharan Other Developing Countries Exposures Ingestion – Animal – Recreational - Insects Incubation Period Laboratory and other tests Medium (10 – 21 days) Long (>21 days) Short (<10 days) Variable (weeks, years) Diagnosis LIKELY SYNDROMES SUSPECTED DIAGNOSIS VACCINATION CHEMOPROPHYLAXIS


Report of Febrile Illness: Report of Febrile Illness About 3 months prior to admission to the hospital patient traveled to Venezuela to see Angel Falls Exposures: freshwater, mosquitoes He received yellow fever vaccination He took malaria chemoprophylaxis You suspect malaria, but patient is not tested because he was given malaria chemoprophylaxis You insist on malaria test, and…. you are correct! Plasmodium vivax detected!