Imported Diseases and Infectious Disease Surveillance

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Imported Diseases and Infectious Disease
Surveillance

• George Turabelidze, MD, PhD
• Missouri Department of Health and Senior Services

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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

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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
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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
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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)

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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

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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

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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

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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

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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 100F (37.8C) 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

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

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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
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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
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Imported Diseases in Relation to Travelers Place
of Exposure

• GeoSentinels 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
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Freedman et al., 2006
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Imported Diseases in Relation to Travelers 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
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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, swimmers itch, impetigo,
  scabies

Modified from Freedman et al., 2006
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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

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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

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

• 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)

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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
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Approaching Public Health Report of Traveler with
Illness

• Person (demographics, vaccinations,
  chemoprophylaxis)
• Place (travel region, exposures)
• Time (travel dates, exposure dates, incubation
  period)

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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

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Chemoprophylaxis for Travelers

• Malaria (doxycycline, mefloquine, cloroquine,
  primaquine, etc.)
• Travelers diarrhea (rifaximin, ciprofloxacin,
  azithromycin)
• Leptospirosis (doxycycline)
• Rickettsiosis (doxycycline)

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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

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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

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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

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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

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Extreme Travelers Risk by Exposure

• Salt water exposure skin infection with
  M.marinum, Aeromonas, V.vulnificus
• Freshwater exposure (including white water
  rafting) leptospirosis, schistosomiasis
• Remote trekking travelers diarrhea,
  rickettsiosis, rabies
• Spelunking (caving) histoplasmosis, rabies
• Cycling rabies

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Incubation Periods of Travel Associated
Infectious Diseases, Short (

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

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Incubation Periods of Travel Associated
Infectious Diseases, Medium (10-21 days)

• Lyme disease
• Malaria
• Measles
• Rickettsiosis
• Typhoid fever
• Viral hemorrhagic fever

• Acute HIV
• American trypanosomiasis
• Babesiosis
• Brucellosis
• Enteric protozoa
• Q fever
• Leptospirosis

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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

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Incubation Periods of Travel Associated
Infectious Diseases, Variable (weeks-years)

• Amebiasis
• Brucellosis
• HIV
• Leishmaniasis
• Malaria

• Melioidosis
• Rabies
• Schistosomiasis
• Tuberculosis

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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!

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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

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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)

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Western blot of pooled mouse antisera to
R.africae human isolate (lane 1), R.africae
tick isolate (lanes 24), R.conorii Kenyan
strain (lane 5), R.conorii Moroccan strain
(lane 6) and Israeli SFG rickettsia (lane 7).
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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 104F, 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.

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Cabin Airflow Patterns

• Sterile air entering
• Heating/cooling
• HEPA filters
• High airflow rates
• Laminar airflow
• Frequent exchanges

World Health Organization, 2006
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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

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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

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ILL TRAVELLERS ASSESSMENT ALGORITHM
Travel Destinations
America Central
America South
Asia Southeast
Asia South Central
Caribbean
Africa Sub-Saharan
Other Developing Countries

• 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

LIKELY SYNDROMES
Exposures Ingestion Animal Recreational -
Insects
VACCINATION
CHEMOPROPHYLAXIS
Incubation Period
SUSPECTED DIAGNOSIS
Medium (10 21 days)
Long (21 days)
Short (
Variable (weeks, years)
Laboratory and other tests
Diagnosis
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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!

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