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Travel Medicine & Insect-borne Illness Bonaire May 2007 Joe Alcock MD MS, NM VAMC, UNM Dept EM A bit about travel medicine Of 100,000 travelers to the developing world in 1 month: 300 will require hospitalization 50 will need air evacuation 1 will die Traveler’s Mortality Cardiovascular 49% Accidental Injury 22% Infectious Disease 1% So don’t smoke & do wear your seat belts! Common Travel Infections Salmonella Shigella Giardiasis Amoebiasis Hepatitis Gonorrhea Malaria Helminth Infestations Complaints of Returned Travelers GI Illness 10% Skin lesions 8% Respiratory 5-13% Fever 3% Non-tropical = majority of fevers Tropical fever = Malaria Source: CDC Yellow Book - www.cdc.gov/travel/yb/index.htm Spring break in Mexico Surfer returns from trip to Mexico, 3 days later - fever 104, retro-orbital headache Doesn’t want to move Persistent nausea & vomiting Exam shows erythematous macular rash that soon becomes confluent. Dengue (Breakbone) fever Flavivirus Single-stranded RNA Widespread in tropics 50-100 mil cases/yr 250-500K hemorrhagic 24K deaths Aedes aegypti Patas blancas Day biter Restless feeder Multiple hosts Anthrophilic 2/3 world population Between 30°N & 20°S Common febrile disease in travelers Dengue increasing Vector likes small collections H2O Habitat for larvae Insecticide Resistance Increasing population Urbanization Fl. Dept Health Classic Dengue Older kids and adults Sudden onset fever Headache, myalgias, arthralgias of shoulders and knees Prostating weakness By 3rd day: rash over thorax, flexure joints Hyperethesia, taste aberration Defervescence Dengue may mimic URI 8 yo boy in Bankok develops mild fever, cough, ST, rash. Misses 1 day of school, returns the next day with no further symptoms and lifelong immunity. In Thailand only 13% miss school in <15 yo group Bangkok ~100% adult seroprevalence > 15 yrs - classic dengue San Salvador, El Salvador Female, 11, falls ill with fever, rash, myalgias, vomiting. 4 days into illness fever begins to decrease. Confusion/somnolence. Hct 38, then 45, then 50. Edema, ascites, RUQ pain B/P 70/34, requires IVF CXR: large effusions, breathing is labored, post-intubation coma briefly precedes death. Dengue Hemorrhagic Fever Rare Typically afflicts patients < 15 years. Diagnostic criteria include: Platelets <100K Evidence of capillary leak, e.g. elevated HCT, ascites of effusions, hypoproteinemia Hemorrhagic manifestations/petechiae Tourniquet Test Checks for hemorrhagic manifestations Inflate blood pressure cuff to median B/P for 5 min or until petechiae are seen: > 3/sq cm Treatment Supportive No ASA/NSAIDs Treat vascular leak with IVF Massive plasma leak may last 48h Correct coagulopathy Death or complete recovery Lab diagnosis has limited clinical utility Elisa tests now available Dengue Prevention No record of epidemic dengue 1946 and 1963 DDT Yellow fever Successful in Argentina, Belize, Bolivia, Brazil, Chile, Colombia, C.R., Equador, Guatemala, Mex, Panama, Uruguay Discontinued in 1970s Aedes aegypti Persisted in Caribbean Islands, Venezuela, and USA. (!) Reinfested countries where once eradicated Dengue outbreak in Jamaica 1977, followed by epidemics until 1981 in every Caribbean island, Central and South America. Experimental Vaccine Development started in 1970s and 1980s at Walter Reed lab All 4 dengue serotypes Live attenuated virus Incomplete immunity may allow DHF if reexposed Meanwhile: Yellow fever Flavivirus carried by Aedes aegypti 200,000 cases/ yr; >20% fatality rate Children, infants at risk Worse in Africa Flu-like to fulminant hepatitis FULMINANT LIVER FAILURE Cytoplamic coagulation in hepatocytes Councilman bodies. Yellow fever endemic areas Yellow Fever New World via Africa in 1600s. Wiped out Carib tribes Maritime trade brings YF to NYC, Boston, Halifax Summer 1793 Philadelphia, city of 50K. YF kills 10% of population. City paralyzed, survivors abandon sick and dying. Yellow Fever in Travelers Epidemic disease 10 cases since 1979 4 of 5 First world cases 1996-2002 visited South America, All fatal Risk to unvaccinated person in endemic area is 1:1000 per month Risk to US travelers = 0.4 -4 in million Yellow Fever Vaccine Live attenuated virus. Contraindicated in immunosuppressed and children less than 4 years Recommended for travel to Amazonian region and parts of Panama. Also equatorial Africa Highly immunogenic/effective. O.5 ml primary and 0.5ml 10 year boosters YF Vaccine Risks Yellow Fever Vaccineassociated viscerotropic disease Clinically & Pathologically = Yellow Fever 23 cases of vaccine disease, 14 fatal, 17% had had thymectomy for thymoma Elderly at risk Malaria, by contrast No Vaccine Malaria kills 1,500,000 yearly Young children and pregnant women Immunity partial and not durable 30,000 travelers: preventable illness 400 million cases worldwide Malaria Case January 2006, a US family w/ 5 kids visit Nigeria Pre-trip: pediatrician gives prn meds only No chemoprophylaxis 3 kids all given Fansidar after fever during trip. Kids felt better 3 had return of fever in US Diagnosed with flu Given antibiotics at the local clinic Then they got sicker Mom notices 1 child is very weak and has yellow eyes! Yellow Kid Conjunctivae icteric Acidosis Hypoglycemia 1 in 20 rbcs parasitized Intubated Transfused All 5 kids tested pos for falciparum malaria Malaria Vector & Pathogen Female Anopheles - Crepuscular hours. Congenital and transfusion - related cases Autochthonous: single mosquito transmits disease from 1 human to another Malaria Parasite Major international public health problem Charles Laveran, a French army surgeon in Algeria, recognized parasites in the blood of a malaria patient in 1880. Nobel Prize in 1907. Role of Mosquitos 1897, Ronald Ross, a Brit in the Indian Medical Service, discovered that mosquitos transmit malaria. For his discovery, Ross was awarded the Nobel Prize in 1902. Major Public Health Problem Variable risk – regional Caused by 4 protozoan species Plasmodium falciparum P. Vivax P. ovale P. malariae Risk to travelers Subsaharan Africa most falciparum cases 500K US travelers to Africa vs. 21 million to other malarious areas. Most malaria in SA and Asia is P. vivax Relative Risk to unprotected travelers: Sub-Saharan Africa -1:50 India - 1:250 S.E. Asia-1:1,000 South America - 1:2,500 Central America -1:10,000 Incubation Following the infective bite: incubation period varies from 7 to 30 days shorter with P. falciparum and longer with P. malariae. Prophylaxis delays symptoms by months, after travelers leave endemic areas. P. vivax and P. ovale: dormant liver stage parasites; may reactivate and cause disease Presenting symptoms Fever Chills Sweats Headaches Nausea and vomiting Body aches General malaise. Exam findings Fever Sweating Weakness Enlarged spleen. In P. falciparum malaria: Mild jaundice Enlargement of the liver Increased respiratory rate. Severe Malaria Cerebral malaria, AMS seizures, coma Severe anemia, hemolysis Hemoglobinuria Pulmonary edema (ARDS), may occur even after treatment Thrombocytopenia Cardiovascular collapse and shock Warning Signs Acute kidney failure Hyperparasitemia, > 5% rbcs infected by parasites Metabolic acidosis Hypoglycemia (low blood glucose), may also occur in pregnant women with uncomplicated malaria, or after treatment with quinine. Malaria Pathogenesis Malaria parasites digest RBC proteins and use glucose to lactic acid as energy, thus hypoglycemia & acidosis. Injure RBC membrane: hemolysis, splenic clearance & anemia. Makes blood cells sticky - obstruct microcirculation Thrombocytopenia - splenic sequestration Treatment Chloroquine Atovoquone/ Proguanil (Malarone) Quinine Sulfate and Doxycycline Mefloquine side effects Combination therapy with Artemesinin P. vivax and malariae mostly chloroquine sensitive Expedition to Amazonia While napping in a remote outpost, this pair wakes up to find pale fleshy bugs on their faces Kissing Bug Barbeiro Vinchuca Reduviidae Triatoma spp. Chagas disease Chagas Disease Carlos Chagas, Brazilian, described the disease in 1909 He discovered the vector: Triatoma bug He named the pathogen, Trypanosoma cruzi, after his mentor, Oswaldo Cruz. Carlos Chagas Oswaldo Cruz Triatoma Chagas is endemic from Mexico to Argentina Transmitted by Triatoma bug - 30 species are vectors. 9 of these vectors are in the US Amazingly the bite is painless! Chagas 16 million infected in Americas 50,000 deaths per year Indolent infections Manifestations after years Cannot be treated once chronic Chagas results when parasite-laden feces of bug are rubbed into eye/cut Food-borne Chagas? Sugar cane juice banned in Brazil Guarapa 25 confirmed cases in Santa Catarina BR 3 deaths Symptoms arose within days - virulent NY Times April 12, 2005 Romana’s sign Hemilateral swelling of face, eyelid, and lymphadenopathy Acute Chagas disease in a Brazilian patient American Trypanosomiasis Parasitemia C-shaped trypomastigotes of T. cruzi are seen in the peripheral blood “Mal de Chagas” African Trypanosomiasis Related trypanosome responsible for African Sleeping Sickness T. gambiense T. rhodesiense Tsetse fly vector Larger than T. cruzi Chagas Disease Amastigote T. cruzi Intracellular Non-flagellated form Indistinguishable from Leishmania Giemsa stain Chagas in Tennessee In 1998,mother of 18 month infant found triatoma bug in crib. Gut contents found to contain Trypanosoma cruzi Infant blood was PCR positive for T. cruzi 2 of 3 raccoons trapped in area tested positive for T. cruzi Herwaldt B.L., et al. (2000) 1998. The Journal of Infectious Diseases 181: 395-399. Chagas in America Animal reservior, T. cruzi, and Triatoma bugs are all abundant Local transmission epidemiology unknown 3 cases of acute Chagas disease have been recorded in US Exact number endemic cases unknown Many more cases are imported Chagas Heart Patients Chagas Heart Syndrome Ventricular Tachycardia, Syncope/Sudden Death, Anginal Chest Pain, Symptomatic AV block, Congestive Heart Failure. EKG suggestive of ischemia CAD mimic, underdiagnosed in US LV aneurysm, regional hypokinesis, many require pacers Hagar J.M. & Rahimtoola S.H. (1991) Chagas' heart disease in the United States. N. Engl. J. Med. 325: 763-768 T. Cruzi myocarditis Amastigote in cardiomyocyte Chronic Chagas Cardiopathy Autopsy of Bolivian Chagas Case Infected cell in center Diffuse lymphocytic infiltration Cardiomyopathy Chagas in US Chronic Chagas Disease reported in Mississippi Seropositivity in US approximately 350,000 with 100,000 cases of chronic disease Megaesophagus, cardiomyopathy common Holbert R.D., et al. (1995) J. Miss. State Med. Assoc. 36: 1-5. Mega GI manifestations Megacolon in Chagas in Bolivia May also affect ureter, bronchus, esophagus, uterus Transfusion Risk In Latin America, blood transfusions are major risk for Chagas transmission ELISA assays are effective at detecting Chagas antibodies in human serum Carvalho MR et al. (1993) Transfusion 33: 830-834 Treatment Drug treatment for acute and congenital cases Nifurtimox and Benznidazole can be used for early chronic phase. T. cruzi antigens stimulate autoimmunity, so no vaccine Travelers can avoid the disease by not sleeping in infested housing. Extra bonus arthropod! Yet another reason to use insect repellent… Bot Fly Torsalo Credit: Marcelo de Campos Pereira Life Cycle When female Dermatobia is ready to oviposit she captures another insect - fly or mosquito - and glues eggs to captured insect's abdomen. Eggs hatch with elevated temperature Dermatobia hominis eggs glued to abdomen of carrier fly. Third Instar Larva Prominent Mouth Hooks Larva in Holstein cow Myiasis caused by Cordylobia anthropophaga Myiasis Second instar larva of C. anthropophaga, an African and Asian fly Adapted to feed on humans In South America, Dermatobia hominis (Bot fly) is man-eating maggot. Bot fly Treatment/prevention Place Tiger Balm or Camphorated Oil over every bite in endemic area Larva needs to breathe Differential Diagnosis of Sebaceous cyst and Infraorbital mass Goodman et al. Arch Ophthalmol. 2000;118:1002-1003 Leishamaniasis Transmitted by Phlebotomus sandfly Asia/Middle East Brazil/South America Returned Military Personnel Leishmaniasis, the “Baghdad Boil” 88 cases 2003 2004 “global struggle against armed extremism” - increasingly exposes Americans to tropical diseases Leishmania Life Cycle The parasites invade the cells of the reticuloendothelial system, such as macrophages, bone marrow cells, speen cells, and the kupfer cells of the liver. Leishmaniasis Leishmaniasis in 88 countries. 350 million people. Rain forests in Central and South America to deserts in West Asia. 90 % visceral leishmaniasis: India, Bangladesh, Nepal, Sudan, and Brazil. Kala Azar Visceral leishmaniasis: fever, weight loss, enlarged spleen and liver Low rbc, wbc, and platelets Espundia Untreated cutaneous leishmania of the face Treatment Sodium stibogluconate Toxic to liver, heart, kidneys Causes rash, pancytopenia, headache, peripheral neuropathy Better to prevent with Deet Summary Classic Dengue: painful, afflicts teens/adults DHF: <15yrs, bleeding and shock Yellow Fever: liver failure, jaundice. Vaccine Malaria; Falciparum fatal, no vaccine, anemia, jaundice, coma, shock. Chagas: indolent, thatch roof, heart & GI, blood transfusions. Bot Fly: excision vs. early petroleum jelly. Leish: Sandfly, skin or visceral, toxic treatment Use protective gear: nets, Deet, Permethrin Travel Resources CDC Yellowbook, International Bulletins www.cdc.gov/travel/ http://www.cdc.gov/travel/yb/index.htm www.cdc.gov/mmwr/international/world.html Travel Health Info Line 877-FYI-TRIP UptoDate Travel Med monograph www.uptodate.com International Society of Travel Medicine www.istm.org/ World Health Organization www.who.int/en/