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Travel Medicine AND Occupational Medicine

WORLD DISEASE PREVALENCE Man Trp Dis, 1996. Wilson, A Guide to Wrld Inf, 1991. CDC 2007.. DiseasePrevalence Deaths/YearTUBERCULOSIS2,000 Million 3 MillionASCARIS1,400EPIDEMIC DIARRHEA ??? 2.2HOOKWORM 900HEPATITIS B 300

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Travel Medicine AND Occupational Medicine

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    1. Travel Medicine AND Occupational Medicine William H. Shoff, MD, DTM&H, CPC Associate Professor of Emergency Medicine Director, PENN Travel Medicine February 27, 2008 Philadelphia Occupational & Environmental Medical Society

    2. WORLD DISEASE PREVALENCE Man Trp Dis, 1996. Wilson, A Guide to Wrld Inf, 1991. CDC 2007. Disease Prevalence Deaths/Year TUBERCULOSIS 2,000 Million 3 Million ASCARIS 1,400 EPIDEMIC DIARRHEA ??? 2.2 HOOKWORM 900 HEPATITIS B 300 1.2 MALARIA 300 3 SCHISTOSOMIASIS 200 0.8 FILARIASIS 130 DENGUE 100 0.025 NEUROCYSTICERCOSIS 50 0.05 AIDS > 40 > 2 MOTORVEHICLE CRASHES > 35 1 TYPHOID FEVER 22 0.2 DRACUNCULIASIS 3.5 (120 M 1991)

    3. Travel Medicine Summary Vaccines - Routine PEDS: DTaP, IPV, Hib, MMR, PCV, Var, HB, Flu, HPV,7Pneu Adult: Tdap, Td, HZost, Flu Adult Special: 23Pneu, HPV, Menin, HA, HB Vaccines - Travel HA, HB, Flu, Polio, Rabies, YF, Menin, JE, Other (??) Food & Water Precautions Cook It, Peel It, Boil It, or… TD, Giard, Amb, HA, Typh, Chol Stand-By Therapy: Cip, Az, Xifax Swim Precautions Lepto, Schisto, Crocodile Insect Precautions Don’t Get Bitten !!! Hat-Long Sl-Pants-S&Shoe Deet & Permethrin Mosquito Nets Malaria Prophylaxis Malarone, Larium, Doxy Driving Precautions Heat & Cold Precautions Animal/Sea Precautions Bear, Lions, Crocs, Sharks, Jellyfish (Box), Snakes Altitude Precautions HAPE & HACE > 8 - 10k Feet Descend-Descend-Descend

    4. 2006 850, 000, 000 People Crossed International Borders 70% Increase Since 1993

    5. Disaster Numbers 1991 – 2000 World Disaster Rep 2001, Int Fed Red Cross/Red Cresent Soc Lancet 2002;360:1083 Natural Disasters: 470 / Yr Killed: 75,000 Affected: 211,000,000 Conflicts: 45 / Yr Killed: > 1.6 million / Yr Collective Violence Interpersonal Self-Inflicted Affected: 31,000,000 / Yr Refugees / Asylum Seekers 12.3 - 15.6 Mill / Year 1994 - 2000

    6. Population Explosion Ehrlich, The Population Explosion, Touchstone, 1990 http://www.ibiblio.org/lunarbin/worldpop 250 million 0 500 million 1650 1,000 million 1850 2,000 million 1930 5,000 million 1990 6,595 million 2006 6,789 million 2008 Feb 26 (303 mill USA, Feb 27, 2008) Rate Increase = 3 Persons / Second

    7. US Travel (Trips) To Foreign Countries Country 1990 1995 2000 2004 Mexico 16.4 Million 18.7 18.8 19.4 W. Europe 8.0 8.2 12.9 11.0 E. Europe 0.3 0.9 0.8 1.2 Caribbean 3.2 3.6 3.9 4.9 South America 0.9 1.6 2.1 2.4 Central America 0.6 0.8 0.9 1.8 Africa 0.3 0.4 0.5 0.6 Middle East 0.5 1.0 1.4 1.0 Asia 2.5 3.6 4.9 5.1 Oceania 0.6 0.6 1.1 8.2 TOTALS 33.3 39.4 47.3 61.9 Developing 34.4 35.5

    8. International Tourism (ARRIVALS IN MILLIONS WORLDWIDE) Dupont & Steffen, Text of Trav Med and Health, Decker, 1997, pp 21-25 World Tourism Association: http://www.world-tourism.org/ 1960 1980 1993 2000 2006 Europe 50 190 298 372 461 Americas 17 61 104 207 136 N. East/So Asia, Oc 0.7 21 69 101 167 Africa 0.6 7 18 24 41 Mid East 0.6 6 7 11 42 S. East Asia 0.2 2 3 6 49 TOTAL 69.1 287 499 721 850

    9. US Travel To Foreign Countries 2004 Profile All US Travel 27.35 Mill Trips Developing Countries Excl Mex 17.1 Mill 817,000 Delaware Valley Purpose Trip Main 2nd Leisure 38% 56% VFR 33 46 Business 22 26 Conven/Conf 2 3 Study/Teach 2 5 Religion/Pilgrm 2 Length Of Stay Average 16.2 D Median 10.0 Number Trips 1 Y 5Y Average 2.8 11 Median 2.0 5 Number Countries Vis 1 81% 2 13 3 + 6 Average # Visited 1.3

    10. Globalization PAST = Numerous Markets, Many Countries TODAY = One Market, The World Multinational Corporations > 35,000 Affiliate Corporations ~ 150,000 Move / Establish Expatriate = $250,000 – $500,000 Repatriate Sick/Injured Expatriate > $600,000

    11. THE ISSUES More Travelers More Vulnerable More Exposure Injury Disease Crime / Terrorism

    12. More Vulnerable FACTORS THAT INCREASE “TRAVELER” RISK Immunological Naivete: MALARIA, HEP A, DENGUE, JAP ENCEPH Waned Immunity: POLIO, DIPHTHERIA, MALARIA PERTUSIS Resident Population Vaccinated: JAP ENCEPH Duration of Trip Contaminated Food and Water

    13. More Vulnerable FACTORS THAT INCREASE “TRAVELER” RISK Indiscriminate Eating Not Protect Skin Walk Barefoot / Sandals Sex Causal 4 - 19% 60% Traveler / Expatriate 40% Native Condum Use Inconsistent 49% None 19% Commercial Sex Worker Sexual Tourism Driving Swimming No Helmets Trek / Tech Climbing Scuba Alcohol & Drugs

    14. Risks that Jeopardize Health Single Ingestion: TRAV DIARRHEA, TYPHOID, BRUCELLOSIS Single Bite: MALARIA, DENUE, YELL FEV, LEISH Single Fresh Water Swim : SHISTO, LEPTO Single Walk Barefoot: STRONGYLOIDIASIS, HOOKWORM, CUT LARVA MIGRANS Single Stroll At Sunset: MALARIA

    15. More Exposures THE DISTRIBUTION OF DISEASE AND INJURY IN TRAVELERS DEATHS TRAVELER’S DIARRHEA MALARIA VACC PREVENT DIS CUTANEOUS LARVA MIGRANS TICK TYPHUS PHYTOPHOTODERMATITIS LEISHMANIASIS SCHISTOSOMIASIS DENGUE TRYPANOSOMIASIS BARTONELLOSIS HEPATITIS E SCUBA DIVING ALTITUDE ILLNESS SAFETY PSYCHO PROBLEMS

    16. Death While Traveling (%) Cause Aust Scot Swiss USA Peace Cor Accident 18 20.7 44 22 70 Hrt Dis 35 68.7 15 49 6 Other/Unk 37 7.0 38 25 10 Infection 2 3.6 3 1 5 Suicide/Hom 8 – – 3 9 Reference Med J Aus Scot Med J Man Trop Ann EM JAMA 1985 1995 1991 Med 12th 1991 254: 1326 163: 27 35: 34 1996, p408 20: 622

    17. MVA-Related Deaths asirt.org/GlobalSafety/Issues/tabid/97/Default.aspx 1 Million Deaths / Yr 85% Developing Countries $500 Billion $60 Billion Developing Countreies 20 - 80 x Developed Countries 23 - 24 Million Injured

    18. Traveler’s Diarrhea THE RISK VARIES WITH DESTINATION Kollaritsch,European J Epid,1989; 5:74

    19. Traveler’ Diarrhea

    20. Traveler’s Diarrhea Begin Anytime Mild to Severe Nausea, Vomiting, Diarrhea, Malaise Duration (Usual): Several Hrs – Few Days Standby Treatment - Take Only If Get Sick Ciprofloxacin Azithromycin Xifaxan Fever, Blood, or Both ? See Doctor

    21. Traveler’s Diarrhea Etiology Enterotoxigenic E. coli (ETEC) Enteradherent E. coli Shigella Salmonella Campylobacter Cyclospora Giardia Amoebiasis Viruses

    22. Food & Water Precautions PREVENT Traveler’s Diarrhea Typhoid Hepatitis A Brucellosis

    23. Food & Water Precautions Boil It, Cook It, Peel It or Forget It Unsafe Tap Water Ice Street Vendors Salads Peeled Fruit Peeled By Someone Else Unpasteurized Milk & Milk Products “Safe” Food Served Piping Hot Too Hot To Eat When Set In Front Of You Treated Water Boiled Chemically Treated Filter + Iodine Resin May Not Get All Viruses Bottled / Carbonated

    24. Malaria Stanley, EM Clinics NA 1997; 15(1):113 Incidence 300-500 million cases / year Deaths 1.5-3.5 million / year 90% Rural Sub-Saharan Children < age 5

    25. Malaria History 1600 - 1700’s Sherman (Ed), Malaria, ASM Pr, 1998

    26. Malaria History – 1946 Traveler’s Malaria, 2001,Decker

    27. Malaria 2002

    28. Malaria US Travelers – 2005 MMWR;June 8, 2007 / 56(SS06) Area # Africa 902 Asia 199 CenAm (No Mex) 116 Oceania 30 Mexico 14 South Am 37 Caribbean 46 Unknown 177 Traveler # Business 55 Missionary 83 Peace Corps 7 Refugee/Immig 4 Sailor/Air Crew 3 Teach/Student 30 Tourist 65 Visit Friend/Relative 488 Other/Mixed Purpose 53 Unknown 82

    29. Malaria Case 65 YO Female ? Trip to Ghana (First time) Daughter Invited Pt to Come Along PMH Negative Saw PCP in Coastal NJ Town Given Typhoid and Hepatitis Vaccines Given Script for Chloroquine and Fansidar Referred to Yellow Fever Center for YF Vaccine Yellow Fever Center Given YF Vaccine & Certificate and Polio Vacc. Not Remember Name of Malaria Prophylaxis And Did Want Not Discuss Matter Further

    30. Malaria Case Uneventful Two Week Trip One Week After Return ? Symptoms Myalgia, HA, Malaise, Fever Saw PCP ? Symptomatic Rx ? Collapsed Three Days ? Admitted to Outside Hospital Malaria Diagnosed After Two-Day W / U Transferred to HUP ICU ? Died 4 Months Later After Stormy Course

    31. 4 Malaria Organisms Plasmodium falciparum Plasmodium vivax Plasmodium ovale Plasmodium malariae

    32. Falciparum Malaria ? 25 % Non-Immune Adults Die < 2 Weeks of Primary Attack... ...IF Untreated

    33. The Malaria Numbers > 2 Billion People Exposed > 600 Million Infections 1 - 3 Million Deaths: Mostly Children Sub-Saharan Africa 60 Minutes = Exposure ? Infected [Lake Louise, Africa] 37 Hours = Initial Syx ? Death [Shortest Interval] 48 Hours ~ Travel Time ? World to Your Practice 7 Days = Shortest Falciparum Incubation < 1 Month After Exposure = Most Cases falciparum Present > 1 Month After Exposure = Most Cases vivax Present 6 Months = Lose Partial Immunity to falciparum 5 Years = Maximal Vivax Relapse

    34. Malaria Life Cycle

    35. Malaria Species Compared Falcip Vivax Ovale Malar Exoerythrocytic (D) 5.5 - 7 6 - 8 9 12 - 16 Prepatent (D) 9 - 10 11 - 13 10 - 14 15 Incubation (D) 12 (7 - 14 - 548) 13 (10 - 17- >365) 17 (6 - 18 - 365) 28 (9-210) RBC’s Invaded All Ages Retics Retics Aging Merozoites / RBC 8 - 24 12 - 24 8 - 12 6 - 12 Earliest Gametes (D) 10 - 15 3 ? ? Merozoites / Tiss Schiz 40,000 15,000 10,000 2,000 Erythrocytic (H) 48 42 - 48 49 - 50 72 Periodicity (H) — ? / 48 ? / 48 ? / 72 Fever Paroxysm (H) 16 - 36 + 8 - 12 8 - 12 8 - 10 Aver Parasit / mm3 > 20,000 10,000 9,000 6,000 Secondary Eryth Cyc – + + – Infection Duration (Y) 1 - 3 1.5 - 5 1.5 - 4 3 - 50

    36. Faciparum Resistance Time To Develop Chlorquine 20 Yrs Pyramethamine < 1 Yr Atovoquone < 1 Yr Proquanil < 1 Yr Mefloquine 6 Yrs

    37. Uncompl Malaria – Syx Traveler’s Malaria, 2001, Decker Syx #Pts % Affected Fever*____________ 1,032________________97_________ Chills 1,243 79 Headache* 1,234 70 Sweating___________ 801________________64_________ Myalgia 826 36 Nausea 777 27 Vomiting 678 27 Diarrhea 1,234 16 Cough 681 13 Abd Pain 1,120 12 Blood In Stool 441 3 *Children & Semi-Immunes

    38. Uncompl Malaria – Sx Traveler’s Malaria, 2001, Decker SX #Pts % Affected Fever 926 81 Splenomegaly 1,061 26 Hepatomegaly 1,056 14 Pallor 487 12 Icterus 1,049 8 Dehydration 323 6

    39. Uncompl Malaria – Lab Lab Test #Pts %Affected ? Plts 1,111 61 ? Bili 750 43 Anemia 1,263 30 Transaminases ? 847 30 Leukopenia 1,262 26 Creatinine ? (> 110) 444 18 Hypoglycemia 573 1

    40. Severe & Complicated Malaria Cerebral Malaria Hypoglycemia Severe Anemia ARDS Shock Renal Failure Hyponatremia DIC Seizures ? Metabolic Acidosis ? Hyperparasitemia % RBC’s Infected Non-Immunes > 2% Immunes > 10%

    41. Malaria - Pathophysiology RBC Destruction Parasitized Cells Innocent By-Stander Cytokines Nitric Oxide Hypoth TNF Stim Synthesis Diffuse Thru Bld-Brain Barrier Disrupt CNS Neurotransmission Sequestration Cytoadherence NOBS On Cells ?

    42. Cerebral Malaria

    43. Malaria In RBC’s THIN SMEAR A. Plasmodium vivax B. Plasmodium ovale C. Plasmodium malariae D. Plasmodium falciparum 1. Ring form (young trophozoite) 2. Trophozoite (growing) 3. Trophozoite (mature) 4. Merozoites 5. Macrogamete 6. Microgamete

    44. Malaria – Treatment Guerrant, Tropical Inf Dis, 1999. Lancet 2004;364:285. Traveler’s Malaria, 2001, Decker. Principles Establish Diagnosis Speciate % Parasitemia Semi -Immune? Area of Acquisition Estimate Resistance Severity? Adm vs Outpt IV vs PO Meds Severe & Complicated Anti-Malarials PO As Soon As Tolerated No Response < 48 Hrs Indicates Therapy Fail Monitor Parasitemia q6 - 8 H Until Decreases Supportive Care

    45. Malaria – Treatment Chloroquine Sensitive — PO Chloroquine* Chloroquine Sensitive — IV/IM Quinine IV or Quinidine* IV Chloroquine IM *Available in USA

    46. Malaria – Treatment Chloroquine Resistant — PO Quinine* Plus Doxy* or Pyrimeth-Sulfadox or Clindamycin* Mefloquine* Halofantrine Malarone™* (Atovaquone + Proguqanil) Plus Doxy Artesunate Plus Mefloquine 8 Other Combinations Outside USA *Available in USA

    47. Malaria – Treatment Chloroquine Resistant — IV/IM Quinine IV / Quinidine IV* Quinine 20 mg/kg salt (16mg base) IV Loading, Then 10 mg/kg salt (8 mg base) q 8-12H IV Loading Leads To More Rapid Parasite Clearance Quinidine 15 mg/kg IV Loading Over 4 Hr Then 7.5 mg/kg IV Over 4 Hr @ 8 Hr Intervals Monitor For QT Prolongation Quinine IM Artemether IM *Available in USA

    48. Malaria – Treatment Multi-Drug Resistant Falciparum Drug Combination* Efficacy Safe Peds Preg Quinine + Tet/Doxy** ++ – – – Quinine + Clindamycin** ++ ++ ++ + Atovoquone + Proguanil** ++ ++ ++ ? Sulfadoxine-Pyrimethamine ± ± ++ ? Artemether + Lumafantrine ++ ± ++ ? Artesunate + Mefloquine ++ ++ ++ ± ________________________________________ * 13 Combinations Total Available Worldwide ** Available In USA

    49. Malaria - Treatment Prevent Relapses of Vivax and Ovale Primaquine If Resistance Occurs, Double Recommended Dose Guerrant et al, Tropical Inf Dis, 1999 Luzzi et al, Lancet 1992; 340:310

    50. Malaria – Differential DX Dengue Influenza Gastroenteritis Hepatitis Hemorrhagic Fevers Leptospirosis Meningitis Bacterial Viral Other Arbovirus Dis Rabies Relapsing Fever Sepsis Syndromes Trypanosomiasis Typhoid Fever

    51. Insect Precautions Don’t Get Bitten ! Long Pants and Sleeves DEET Long-Acting Forms Better Sawyer Controlled Release™ Ultrathon™ Minimal Absorption Minimal Evaporation Equivalent To 80% Regular DEET Safe With Children If Not Use Long-Act, Use 30 - 35% Regular Product Color Of Clothes Mosquitoes Attracted To: Blue, Black, Red Not Attracted To Khaki, Tan, Pale Green Mosquito Nets Work !! If No Holes If Not Touch Skin Better If Permethrin Impregnated

    52. Insect Precautions Don’ t Get Bitten Avoid Scented Products Soap Perfume Deodorant Shampoo Ineffective Skin So Soft™ Mosquito Coils Alone Screens With Holes Mosquito Proof Bedroom Close Up Room Spray Insecticide High On Walls By Ceiling Behind Curtains High In Closets Keep Room Closed x 2 Hr Air Out Room x 1 Hr Before Sleeping

    53. Vaccines – General Issues Type: Live Or Not Live Efficacy: How Well It Protects Age Admin: What Ages Can It Be Given Schedule: How Given To Achieve 1ş Immunity Protect: How Many Years Until Booster Needed Pregnancy/Lactation: Is It Safe In Pregnancy And With Breast Feeding Disease Morbidity / Mortality: What Is The Vaccine Preventing

    54. Vaccines For Travel Hepatitis A Hepatitis B Influenza Japanese Encephalitis Meningococcal A, C, Y, W-135 Pertussis Pneumoccal Polio Rabies Typhoid Yellow Fever Other Vaccines To Consider Varicella Herpes Zoster HPV

    55. Hepatitis A 2002 CDC – http://www.cdc.gov/travel/diseases/hav.htm

    56. Hepatitis A Vaccine Inactivted (Not Live) Efficacy 94 - 99% Age Administer > 1 year Adverse React: Mild Local Or Systemic Syx Schedule: 0, 6-12 Mos Protect: Life Preg/Lact: No Studies. Use If Indicated. Hep A Morbidity / Mortality: Fulminant Hepatitis > 2% Age 50

    57. Hepatitis B 2002 CDC – http://www.cdc.gov/travel/diseases/hbv.htm

    58. Hepatitis B Vaccine Recombinant (Not Live) Efficacy > 90% (Age < 40 Yr) 65-75% (Age 60) 1st Dose 30 - 55%; 2nd Dose 75% Age Administer > Birth Adverse React: Mild Local Or Systemic Syx Schedule: 0, 1, 6 Mos Protect: Life Accelerated: 0, 1, 2 Mos + Booster 12 Mos Preg/Lact: Use If Indicated Hepatitis B Morbidity / Mortality: Hepatocellular Cancer Chronic Active Hepatitis

    59. Twinrix – Hep A + Hep B Type: Not Live Combination: Havrix® + Engerix® (GSK) Efficacy: Hep A 99.6 - 100%; Hep B 95 - 100% Age Admin: ? 18 Yrs Schedule: 0, 1, 6 Mos Accel: 0, 7, 21 Da Bst 1 Yr Protect: Life Preg/Lact: No Studies; Use If Indicated Disease Morbidity / Mortality: See Hep A & Hep B

    60. HPV Vaccine (6, 11, 16, 18) Type: Not Live Efficacy: High (Pvt: Persising HPV Inf, Precursor Lesions of Cervical/Vaginal/Vulvar Cancer, Genital Warts) Age Admin: 11 - 12 Yrs (Young As 9 Yrs) Catch-Up 13 - 26 Yrs Schedule: 0, 2, 6 Mos Protect: [Ongoing Studies] Pregnancy/Lactation: Preg - Not Rec (Limited Data) Lactation - Safe Disease Morbidity / Mortality: Cervical Cancer, Other Anogenital Cancers, Genital Warts

    61. Human Papilloma Virus 100 Types, > 40 Infect Genital Area 16 Types Carcinogenic Cervical & Anogenital Cancers Account For 99% Cervical Cancer #16 & #18 Account For 70% Note: Majority Women Inf HPV Not Devel Cervical Cancer #6 & #11 Assoc 90% Genital Warts

    63. Japanese Encephalitis Vaccine Inactivated (Not Live) Efficacy 91% Age Administer > 1 Yr Adverse React: Local Syx (20%) Sytemic Syx (10%) Urticaria / Angioedema Reported In Past ? ? Now With More Purified Vaccine Schedule: 0, 7, 14/30 Da Protect: 2 Yr Preg/Lact Avoid Trimesters 1-2 Unless ? ? Risk JE Trimester 3 And Lactation: Use If Indicated Symptomatic JE Morbidity / Mortality Death 5-30% Neuro 33-50%

    64. Meningococcal Meningitis

    65. Meningoccal Vaccine (A, C, Y, W-135) Polysaccharide (Not Live) Efficacy 100 % Age Administer > 2 Yr Adverse React: Mild Local Or Systemic Syx Schedule: 1 Injection Protect: 3 Yr Preg/Lact: No Doc Adverse Effects. Use If Indicated. Meningococcal Disease Morbidity / Mortality: Fulminant 18-70% Less Fulminant < 10%

    66. History of Pertussis Bordetella persussis 1st Outbreak Described 1578 Paris –De Baillou Quinte 5 hr period periodicity of cough United States Before Vaccine 270,000 Cases / Yr 10,000 Deaths After Vaccine 1976 – 1010 Cases 1996 – 7796 Cases Worldwide 1994 40 Mill Cases 5 Mill Pneumonias 360,000 Deaths 50,000 w/ Permanent Neuro Deficits Organism Grown 1906 Jules Bordet & Octave Gengou Crude Vaccines Followed

    67. Reported Pertussis by Age, 1980-2004*

    68. Pertussis Among Adolescents Pneumonia (2%) Rib fractures (1%) Hospitalization (~1%) Medical costs Missed school and work Impact on public health system

    69. “Pertussis Vaccine” – TdaP Type: Not Live Efficacy: 92% (Pertusis in Adolescents/Adults) Age Admin: 10 - 18 Yr (GSK) 11 - 64 Yr (SP) Schedule: Single Dose Protect: Unk, Probably Many Yrs Pregnancy/Lactation: Pregnancy C. Give Only If Necessary. No Reproduction Studies. Disease Morbidity / Mortality: Protracted Illness With Time Loss. Severe Cough Fx Ribs. Deaths Occur Outside US

    70. Pneumoccal Disease Pneumoccal Polysaccharide Vaccine 23-Valent Licensed 1983 Isolates From Serious Infections Covered In 90% Multi-Drug Resistant Organisms In Many Countries Invasive Disease Mortality Bacteremia 5 - 36% All Ages 18 - 51% Age > 65 Meningitis 20 - 40%

    71. Polio 1 Time Adult Booster Child - 10 Yr After Last Dose Cases Endemic Africa: Nigeria Asia: Afghanistan, India, Pakistan Imported Africa: Angola, Cameroon, Congo, Ethiopia, Kenya, Namibia, Niger, Somalia, Yemen Asia: Bangladesh, Indonesia, Nepal Paralytic Polio Etiol Wild Type PV - 1, 2, & 3 Circulat Vacc Derived PV cVDPV Countries Egypt 1983 - 1993 Haiti / Dom Rep 2000 Philippines 2002 Vaccine Assoc Paralytic PV VAPP Risk 1 Case / 3 Mill Doses

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