Ill Returning Travelers PDF

Ill Returning Travelers Lin H. Chen, MD, FACP, FASTMH, FISTM Director, Mount Auburn Travel Medicine Center Associate Professor of Medicine, Harvard Medical School Lecturer, MIT Immediate Past President, ISTM ISTM Review and Update Course, February 2022 Disclosures • Relationships with commercial i...

Ill Returning Travelers Lin H. Chen, MD, FACP, FASTMH, FISTM Director, Mount Auburn Travel Medicine Center Associate Professor of Medicine, Harvard Medical School Lecturer, MIT Immediate Past President, ISTM ISTM Review and Update Course, February 2022 Disclosures • Relationships with commercial interests: - Advisor/Consultant: Shoreland, Valneva, Takeda, Emergent, Sanofi-Pasteur - Data Safety Monitoring Board: Valneva - Royalties: “Infectious Diseases: A Geographic Guide” Objectives ! Provide key epidemiologic background on travel-related illnesses ! Discuss approach to ill returning travelers ! Highlight some frequently encountered diagnoses Proportion of travelers with specific health issues during travel, 1987 - 2016 Steffen 1987 % (N = 7,886) Hill 2000 % (N = 784) Chen 2016 % (N = 628) Ill Saw a doctor 15 2.7 64 8 49 7 Hospitalized 0.5 <1 1 Diarrhea Fever Accident/Injury 8.5 1.9 0.5 46 3 5 27 5 3 Steffen R. JID 1987; Hill DR. JTM 2000; Chen LH et al. TMID 2016 Study Top illnesses (%) % sought Hospitalization medical care (%) Chen et al (2016) n=400 Diarrhea (52), headache (26), fatigue (25), cough (24), runny/ stuffy nose (24), fever/shaking/chills (16) 18 <1 Wilkman et al (2016) n=363 TD, skin problem, fever, vomiting, respiratory infection NA 1 Balaban et al (2014) n=33 Diarrhea (21), sore throat (11), nausea/vomiting (9), congestion/runny nose (8), coughing (7) 19 3 Dia et al (2010) n=313 Arthropod bite (62), diarrhea (46), sunburn (36), vomiting (9), cough (8) 11 <1 Rack et al (2006) n=282 GI (81), respiratory (32), fever (15), dermatologic (10) 16 <1 Hill (2000) n=501 Diarrhea (46), respiratory symptoms (26), skin (8), high altitude sickness (6), motion sickness (5) 8 3 Steffen et al (1987) n=1209 Severe diarrhea (56), vomiting/abd cramp (26), common cold (14), high fever several days (13), dermatosis (8) 55 1 Steffen et al (1985) n=7906 Diarrhea, constipation, respiratory infections, insomnia, headache NA NA Angelo KM et al. JTM 2017;1-8. Study n=travelers ill Top illnesses (%) % sought Hospitalization medical care (%) Chen et al (2016) n=400 Diarrhea (52), headache (26), fatigue (25), cough (24), runny/ stuffy nose (24), fever/shaking/chills (16) 18 <1 Wilkman et al (2016) n=363 TD, skin problem, fever, vomiting, respiratory infection NA 1 Balaban et al (2014) n=33 Diarrhea (21), sore throat (11), nausea/vomiting (9), congestion/runny nose (8), coughing (7) 19 3 Dia et al (2010) n=313 Arthropod bite (62), diarrhea (46), sunburn (36), vomiting (9), cough (8) 11 <1 Rack et al (2006) n=282 GI (81), respiratory (32), fever (15), dermatologic (10) 16 <1 Hill (2000) n=501 Diarrhea (46), respiratory symptoms (26), skin (8), high altitude sickness (6), motion sickness (5) 8 3 Steffen et al (1987) n=1209 Severe diarrhea (56), vomiting/abd cramp (26), common cold (14), high fever several days (13), dermatosis (8) 55 1 Steffen et al (1985) n=7906 Diarrhea, constipation, respiratory infections, insomnia, headache NA NA Angelo KM et al. JTM 2017;1-8. Study n=travelers ill Top illnesses (%) % sought Hospitalization medical care (%) Chen et al (2016) n=400 Diarrhea (52), headache (26), fatigue (25), cough (24), runny/ stuffy nose (24), fever/shaking/chills (16) 18 <1 Wilkman et al (2016) n=363 TD, skin problem, fever, vomiting, respiratory infection NA 1 Balaban et al (2014) n=33 Diarrhea (21), sore throat (11), nausea/vomiting (9), congestion/runny nose (8), coughing (7) 19 3 Dia et al (2010) n=313 Arthropod bite (62), diarrhea (46), sunburn (36), vomiting (9), cough (8) 11 <1 Rack et al (2006) n=282 GI (81), respiratory (32), fever (15), dermatologic (10) 16 <1 Hill (2000) n=501 Diarrhea (46), respiratory symptoms (26), skin (8), high altitude sickness (6), motion sickness (5) 8 3 Steffen et al (1987) n=1209 Severe diarrhea (56), vomiting/abd cramp (26), common cold (14), high fever several days (13), dermatosis (8) 55 1 Steffen et al (1985) n=7906 Diarrhea, constipation, respiratory infections, insomnia, headache NA NA Angelo KM et al. JTM 2017;1-8. 2013;158:456-468 2007-2011; n=42,173 Top exposure regions: Asia (33%), sub-Saharan Africa (27%) ¾ of travel-related illness was due to: -Gastrointestinal diagnoses (34%) -Febrile illness (23%) -Dermatologic disorder (20%) Top specific causes for GI, febrile, dermatologic, respiratory illnesses by region Leder et al. GeoSentinel surveillance of illness in returned travelers, 2007-2011. Ann Int Med 2013 Vaccine preventable disease travel health risks: estimated incidence per month in lower income countries among non-immunes Steffen R. Travel vaccine preventable diseases—updated logarithmic scale with monthly incidence rates J Travel Med. 2018;25(1). doi:10.1093/jtm/tay046 Hufnagel L et al. PNAS 2004 Febrile systemic illness n=2,451 Wilson ME et al. CID 2007. Many possible causes of fever after travel Consider: ! Some are life threatening • Unrelated to recent trip ! Many are unfamiliar • Infection with common, ! Initial presentation of selfwidely distributed pathogen limited infection and • Related to en-route exposure progressive, lethal infection • From forgotten travel may be identical • Associated with past travel ! Refer to clinicians with • May not be infection ID/tropical medicine expertise Age Relevant history: host Underlying diseases Past infections Vaccines, drugs, chemoprophylactic agents Chronology of symptoms Relevant history: destination ! Location ! Season ! Duration of stay ! Accommodations ! ID profile of area, including recent outbreaks Relevant history: activities ! Food & drink ! Arthropod bites ! Use of repellents, bednets, screens ! Possible blood/body fluid exposure (sex, shaves, injections, dental work, medical treatment) ! Animal contact (bites, scratches, licks) ! Water (fresh/salt), soil ! Caves Correlate incubation period with history to generate differential diagnoses • • • • • • • • • • <14 days 14 days to 6 weeks Acute HIV Dengue, chikungunya, Zika Enteric fever Encephalitis, arboviral Influenza Legionellosis Leptospirosis Malaria: P. falciparum Spotted fever rickettsiae 2022: Covid-19 • • • • • • • • • Encephalitis, arboviral Enteric fever Acute HIV Leptospirosis Malaria: P. vivax Hepatitis A Hepatitis E Amebic liver abscess Acute schistosomiasis >6 weeks • Amebic liver abscess • Hepatitis E • Malaria • Acute schistosomiasis • Hepatitis B • Leishmaniasis, visceral • TB Use all information to generate and limit differential diagnoses Geographic distribution of diseases Host Exposures, activities Incubation of infections and time since exposures Clinical and laboratory findings Common clinical findings in febrile patients Fever + rash Fever + abdominal pain Fever + normal or low white blood cell count Fever + hemorrhage Fever + arthralgia or myalgia (sometimes persistent) Fever + eosinophilia Fever + respiratory symptoms/ pulmonary infiltrates Fever + altered mental status/central nervous system involvement Fever + jaundice Mononucleosis syndrome Wilson ME. Fever. In Health Information for International Travel 2020. Fever + rash: in 2022 also consider Covid-19 Dengue Zika Chikungunya Measles Rickettsial infections Enteric fever Meningococcemia Acute HIV Vesicular rash: • Monkeypox, Rickettsia, varicella, smallpox, disseminated vaccinia Drug reactions www.aad.org Chikungunya Burt FJ et al. Lancet ID 2017 37 yo F noted low grade fever and lesions on arm 2 days after return from 2-week safaris in South Africa, Zimbabwe, Zambia. The likely diagnosis is: A. B. C. D. Buruli ulcer African tick bite fever Schistosomiasis Monkeypox 37 yo F noted low grade fever and lesions on arm 2 days after return from 2-week safaris in South Africa, Zimbabwe, Zambia. The likely diagnosis is: A. B. C. D. Buruli ulcer African tick bite fever Schistosomiasis Monkeypox African tick bite fever ! Cause: Rickettsia africae ! Widely distributed in Africa • GeoSentinel: rickettsial disease is 2nd only to malaria as a cause of fever in travelers from subSaharan Africa ! Sporadic, clusters in travelers ! Eschars multiple (54%) ! Regional adenopathy (42%) ! Among patients with rash • 51% mac-pap, 45% vesicular, 4% purpuric Rickettsial infections Parola P , and Raoult D Clin Infect Dis. 2001;32:897-928 © 2001 by the Infectious Diseases Society of America Measles Measles re-emergence https://www.cdc.gov/measles/cases-outbreaks.html Year Outbreak notes 2011 Increased in >30 countries in Europe; France large outbreak 2013 159 cases from 16 states; 99% importassociated; 50% Europe 2014 23 outbreaks; Ohio unvaccinated Amish; ex. Philippines 2015 Disneyland, imported virus B3; identical to 2014 Philippines 2018* 17 outbreaks; Orthodox Jewish unvaccinated; ex. Israel Fever + abdominal pain • Invasive enteropathogens • GeoSentinel: specific bacteria especially related to SE Asia, SSA, Middle E, N Africa • Campylobacter • Salmonella • Shigella ! Enteric fever ! Amebic or pyogenic liver abscess ! Hepatitis ! 2022: Covid-19 Leder et al. Ann Int Med 2013 Fever + normal or low white blood cell count ! Dengue ! Chikungunya ! Zika ! Acute HIV ! Malaria ! Rickettsial infection ! Enteric fever ! 2022: Covid-19 Fever + hemorrhage ! Dengue ! Meningococcemia ! Leptospirosis ! Rickettsial infections ! Yellow fever ! Other viruses, including Ebola, Lassa, CrimeanCongo, hantaviruses, Rift Valley, Marburg… Fever + arthralgia or myalgia ! Chikungunya ! Dengue ! Zika ! Ross River virus ! Muscular sarcocystosis ! Trichinellosis ! 2022: Covid-19 From Powers AM. In Hunter’s 33 yo M with fever, arthritis, psoriasis flare Mayo Clin Proc 2019 Fever + eosinophilia ! Acute schistosomiasis ! Drug hypersensitivity reaction ! Fascioliasis ! Sarcocystosis ! Trichinellosis ! Angiostrongyliasis ! and other parasitic infections (rare) Fever + respiratory: must consider Covid-19 ! Covid-19 ! Influenza ! Legionnaires disease (cruises, hotels, spas, many areas) ! MERS-CoV ! Q fever (Coxiella burnetti) ! Hemorrhagic pneumonia with leptospirosis ! Fungal: coccidioidomycosis (e.g. Mexico hotel construction, archeologic dig), histoplasmosis (e.g. Mexico, trek through tunnel, spelunking, excavation) Fever + mental status change/CNS ! Cerebral malaria ! Arboviral encephalitides (e.g. Japanese encephalitis, WNV) ! Meningococcal meningitis ! Rabies ! African trypanosomiasis ! Scrub typhus (Orientia tsutsugamushi) ! Angiostrongyliasis (rat lungworm) ! Tickborne encephalitis • • • • Acute HIV Murray Valley encephalitis Dengue, Zika, chikungunya 2022: Covid-19 Fever + jaundice ! Acute viral hepatitis (A, B, C, E) ! Yellow fever and other hemorrhagic fevers ! Severe malaria ! Leptospirosis ! LFT abnormalities: Covid-19 frequently associated with transaminitis Leptospirosis ! ! ! ! ! Zoonosis Global distribution Spirochete Fresh water Incubation: 2-20 d Clinical presentation: • Fever • Headache • Chills • Myalgia • Vomiting • Jaundice • Conjunctival suffusion • Abdominal pain • Diarrhea • Rash Mononucleosis syndrome CMV (cytomegalovirus) EBV (Epstein-Barr virus) Toxoplasmosis Acute HIV infection Long Covid Undifferentiated fever ! Many diagnoses fall into this category even though some may be associated with syndromes or affect particular systems ! 2022: consider Covid-19 • • • • • • • • • • • Malaria Dengue Chikungunya Enteric fever Other GI pathogens Rickettsial disease Leptospirosis Influenza, CMV, EBV Acute HIV Amebic liver abscess Zika Malaria: difficult diagnosis ! Signs and symptoms nonspecific ! Patient may be afebrile with unremarkable exam when seen ! Parasites may be sequestered in deep tissues; few on peripheral smear ! Many labs lack expertise in diagnosis ! Severe malaria treatment: artesunate from CDC Malaria: US surveillance ! 2017: 2,161 cases reported (2016 had 2,078, prior highest since 1971*) • 79% P. falciparum, 11% P.vivax • 84% acquired in Africa ! Top countries of exposure 2017 • Nigeria • Sierra Leone • Cameroon • Ghana • Liberia • Reason for travel • VFR 73% • Missionary 8.8% • Business 8.5% • Tourism 5.8% • Education 2.6% • 14.4% severe • 7 deaths CDC. Malaria surveillance – US, 2017.MMWR 2021; 70(2) Malaria diagnosis ! RDT (rapid diagnostic test), microscopy, PCR ! If initial smear negative, REPEAT! ! Request thick and thin; results TODAY ! Need to know: • Malaria: yes or no • Species • Parasitemia (≥5% considered severe) • Can patient take oral meds ! CDC Malaria Hotline • 770-488-7788 (M-F, 9am-5pm) • toll-free 855-856-4713 ! CDC Emergency Operations Center • 770-488-7100 (evenings, weekends, holidays) ! Is artesunate indicated? Licensed 2020, commercially available Potential Ae. aegypti & Ae. albopictus distribution based on present climate conditions Kamal M et al. PLOS ONE 2018:13(12); e0210122. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0210122 Dengue ! Family Flaviviridae, genus Flavivirus ! Mosquito-borne: Aedes ! Widespread in tropical/subtropical areas ! 4 serotypes ! Present in urban and rural areas ! GeoSentinel: Dengue is the most common febrile illness from every region except subSaharan Africa Dengue ! Incubation: 4-7 days (3-14 days) ! Clinical: acute fever, headache, retroorbital pain, myalgia, arthralgia, bone pain, rash, petechiae… ! Severe: vascular permeability/plasma leakage, hemoconcentration • Risk for severe dengue increased ~100x with 2nd infection • Virulence may also vary by genotype ! CFR <1% with good care ! Diagnosis: PCR, NS1, IgM, IgG Dengue, chikungunya, Zika Incubation period (d) Asymptomatic Clinical: Fever Headache Retroorbital pain Rash Conjunctivitis Arthralgia/arthritis Myalgia Petechiae Dengue 3-14 75% Chikungunya 1-12 25% Zika 1-12 50-80% +++ +++ +++ +++ ++ + +++ +++ +++ + + + + +++ ++ + + + + +++ +++ + ++ + Chikungunya virus ! Family Togaviridae, genus Alphavirus: single-stranded, enveloped RNA ! Mosquito-borne: Aedes ! Identified 1952 Tanzania, border Mozambique, febrile patient ! 3 lineages per E envelope: West African, East Central South African, Asian ! Disease burden: large sporadic outbreaks ! Clinical: arthritogenic; “that which bends up” ! Prevention: personal protective measures Chikungunya virus: clinical ! ! ! Incubation: 3-7d (range 1-12d) Asymptomatic <25% (some series 5-18%) • Acute (0-3wk): fever >90%, symmetrical polyarthralgia >80%, pain/myalgia/rash 36–64% • Post acute (4-12wk): joint pains x4-10 wks in middle age, longer in elderly • Chronic (>12wk): in 15->50%, symmetrical arthritis/arthralgia CFR 0.01-0.1% https://www.cdc.gov/chikungunya/geo/index.html PAHO: Cases of Chikungunya Virus Disease US CHIKV cases By Country or Territory Cumulative Cases 2021 Year Total cases 2019 184,789 2020 103,002 2021 (Sept 30) 106,802 2014 2799 2015 895 2016 248 2017 156 2018 116 2019 192 2020 33 https://www.cdc.gov/chikungunya/geo/united-states.html Zika ! Family Flaviviridae, genus Flavivirus: single-stranded, enveloped RNA ! Transmission: Aedes • Other: sexual, vertical (congenital Zika syndrome), blood ! Disease burden: epidemics; 31,587 cases in Americas 2018 (Brazil 19,020, Panama 2752, Bolivia 1736, Cuba 873) ! Clinical: most asymptomatic; fever, rash, conjunctivitis, myalgia; neurotropism with significant Guillain-Barre syndrome ! Prevention: personal protective measure Zika: clinical ! Incubation: 2-7 days (range 1-12 days) ! Asymptomatic: Yap 80% asymptomatic (Duffy et al) • French Polynesia: 29-53% asymptomatic (Aubry et al) ! Symptoms • Rash, conjunctivitis • Fever – usually 2 days • Arthralgia, myalgia - up to 1 week ! Adults and children infected postnatally: similar Zika: clinical ! Incubation: 2-7 days (range 1-12 days) ! Asymptomatic: Yap 80% (Duffy et al) • French Polynesia 29-53% (Aubry et al) ! Symptoms • Rash, conjunctivitis • Fever 2 days, headache • Arthralgia, myalgia - up to 1 week ! Complications: neurologic (GBS, myelitis, meningoencephalitis, neuropathy), autoimmune, congenital Zika syndrome ! Children infected postnatally: similar to adults PAHO: Cases of Zika virus disease by country or territory Cumulative cases 2021 Year Total cases 2019 35,917 2020 22,885 2021 (Sept 30) 12,564 US Zika cases (ArboNET data 1/19/22) Year 2015 2016 2017 2018 2019 2020 US States Locally acquired** 0 224 7 0 0 0 US States Travel-associated† 62 4,944 445 74 28 4 Pregnancy & Infant Registry: (as of 10/31/18) US Territories Locally acquired 9 36,367 665 147 73 57†† US States+DC: 2,490 cases US Territories: 4,917 cases US Territories Travel-associated 1 145 1 1 1 0 Table 11-07. Ten most common skin lesions in returned travelers, by cause Dermatologic problems after travel CDC Yellow Book 2020 Karolyn A. Wanat, Scott A. Norton Skin lesion % of all derm dx (n = 4,742) Cutaneous larvae migrans 9.8 Insect bite 8.2 Skin abscess 7.7 Superinfected insect bite 6.8 Allergic rash 5.5 Rash, unknown origin 5.5 Dog bite 4.3 Superficial fungal infection 4.0 Dengue 3.4 Leishmaniasis 3.3 Myiasis 2.7 Spotted-fever group rickettsiae 1.5 Scabies 1.5 Cellulitis 1.5 43 yo F presents with skin lesion on arm, painless x 2-1/2 months. Onset soon after a 2-week trip to Limon, Costa Rica. What is the diagnosis? A. B. C. D. Infected mosquito bite Myiasis Leprosy Leishmaniasis 43 yo F presents with skin lesion on arm, painless x 2-1/2 months. Onset soon after a 2-week trip to Limon, Costa Rica. What is the diagnosis? A. B. C. D. Infected mosquito bite Myiasis Leprosy Leishmaniasis Cutaneous Leishmaniasis ! Papule, nodule, painless ulcer with rolled edges ! Other presentations • Multiple lesions • Nodules; satellite lesions • Plaques • Nodular lymphangitis; regional adenopathy Leishmania Viannia panamensis 5/31/11 5/3/11 6/17/11 6/21/11 6/7/11 7/26/11 6/14/11 8/1/11 26 yo M presents with itchy rash 10 days after return from 8-day resort trip to Jamaica. What is the diagnosis? A. B. C. D. Tungiasis Jellyfish sting Cutaneous larva migrans Myiasis (photo courtesy Jay Keystone, in Wilson CID 2014) 26 yo M presents with itchy rash 10 days after return from 8-day resort trip to Jamaica. What is the diagnosis? A. B. C. D. Tungiasis Jellyfish sting Cutaneous larva migrans Myiasis (photo courtesy Jay Keystone, in Wilson CID 2014) 50-year-old M returned from Belize feeling stabbing pain and movement within his arm lesions A. B. C. D. (photo courtesy Jay Keystone, in Wilson CID 2014) Leishmaniasis Jellyfish sting Cutaneous larva migrans Myiasis 50-year-old M returned from Belize feeling stabbing pain and movement within his arm lesions A. B. C. D. (photo courtesy Jay Keystone, in Wilson CID 2014) Leishmaniasis Jellyfish sting Cutaneous larva migrans Myiasis Tungiasis: 21-year-old woman returned from Peru with painful nodules on her toes. (photo courtesy Jay Keystone, in Wilson CID 2014) Mark your calendars.…