International travel ~1 billion travelers cross international - PDF document

Infections in Returning Travelers Brian Schwartz, MD Professor of Medicine UCSF, Division of Infectious Diseases International travel • ~1 billion travelers cross international boarders annually • 60 million travel from the US – Half to developing countries

Travelers crossing international borders Keystone. Travel Medicine. 2008 Why do people travel from the US? Service Work 15% Research/Education Leisure 9% 50% Visiting Friends and Relatives 11% Business 15% N=13,235 Larocque R. Clin Infect Dis . 2011

Travel related morbidity/mortality? • 20-70% report some illness • 1-5% seek medical attention • 0.05% evacuation Hill DR. CID. 2006 Top 5 complaints in returning travelers leading to MD visit • Fever • Acute diarrhea • Dermatological disorders • Chronic diarrhea • Nondiarrheal gastrointestinal disorders Freedman DO. NEJM. 2006.

Top 5 complaints in returning travelers leading to MD visit • Fever • Acute diarrhea • Dermatological disorders • Chronic diarrhea • Nondiarrheal gastrointestinal disorders Freedman DO. NEJM. 2006. Case 29 y/o presents to urgent care with fever and myalgias for 3 days. He returned 4 days ago from a 3-week trip to Bangladesh. He is working for an NGO creating sustainable housing.

Infection risk in How do you area traveled think about Exposures/ determining Prevention? the cause of Incubation Signs, period? fever and 1 st day in risk symptoms, area to onset labs? rash in a of symptoms returning traveler? Question Why you are asking Where? Geographic disease association Vaccination/prophylaxis? Helps narrow/influence DDx Consumption (food/H 2 0) TD, giardia, Hep E/A, flukes, etc. Immune status? Alters risk of infections Fresh water? Leptospirosis, schistosomiasis Skin to soil? Strongyloides, cutaneous larva migarns Insect bites? Malaria, viruses, ATBF, etc…. Animal exposure/bites? Rabies, brucella, etc. Other ill travelers? TB, VZV, etc… Sex, tattoos, piercing? HIV, HCV, HBV, syphilis, GC, etc.

Fever in a returning traveler Higher level of care setting Severe illness Febrile Assessment • Acute schisto and/or returning • DRESS based on signs/ malaria traveler symptoms risk Initial lab testing • Dysentery • Check CBC w/ diff • E histolytica • Dengue • LFTs, Chem 7 • Zika • Malaria smear • Chikungunya • Hepatitis A, E > B, C • Other testing PRN • Rickettsial • Influenza • EBV, CMV • Malaria • Acute schisto • Bact PNA • Typhoid fever • TB • Measles • Acute EBV, CMV, HIV • Histo/Cocci Fever in a returning traveler Higher level of care setting Severe illness Febrile Assessment • Acute schisto and/or returning • DRESS based on signs/ malaria traveler symptoms risk Initial lab testing • Dysentery • Check CBC w/ diff • Dengue • E histolytica • LFTs, Chem 7 • Zika • Malaria smear • Chikungunya • Other testing PRN • Rickettsial • Hepatitis A, E > B, C • Influenza • Malaria • EBV , CMV • Acute schisto • Bact PNA • Typhoid fever • TB • Measles • Acute EBV , CMV, HIV • Histo/Cocci

Use resources • CDC travel website • WHO website • http://healthmap.org • GeoSentinel articles Destination: Etiology of fever according to region traveled 1000 900 Freedman DO. NEJM. 2006. 800 700 Unknown Rickettsia 600 Cases Malaria 500 Typhoid 400 EBV/CMV 300 Dengue/Chikungunya/Zika Dengue/Chikungunya/Zika 200 100 0 Carribean C. America S. America Sub ‐ Saharan South Central SE Asia Africa Asia

Etiology of fever according to interval after travel 100% Other 90% Rickettsia CMV/EBV Proportion of Diagnoses Malaria 80% Other 70% Dengue/Chikungunya/Zika Typhoid 60% P. vivax 50% 40% 30% P. falciparum 20% 10% 0% 0 ‐ 7 7 ‐ 14 14 ‐ 21 21 ‐ 28 28 ‐ 35 35 ‐ 42 >42 Days post ‐ travel Wilson ME. CID. 2007. Causes of fever in traveler by incubation period Causes of fever in traveler by incubation period Incubation Common causes Incubation Common causes Bacterial: Rickettsia Short Bacterial: Rickettsia Short Viral: Dengue, Chikungunya, Zika, Yellow fever (< 7 d) Viral: Dengue, Chikungunya, Zika, Yellow fever (< 7 d) respiratory viruses respiratory viruses Bacterial: Lepto, typhoid fever, GC, syphilis Intermediate Bacterial: Lepto, typhoid fever, GC, syphilis Intermediate Fungal: Acute histo or cocci (8-30 d) Fungal: Acute histo or cocci (8-30 d) Viral: acute HIV, CMV, EBV Viral: acute HIV, CMV, EBV Protozoal: Plasmodium species, E histolytica Protozoal: Plasmodium species, E histolytica Helminthic: Acute Schisto Helminthic: Acute Schisto Bacterial: TB Long Bacterial: TB Long Viral: acute HIV, CMV, EBV (> 30 d) Viral: acute HIV, CMV, EBV (> 30 d) Protozoal: P ovale, P vivax, Leish, Amoebic abscess Protozoal: P ovale, P vivax, Leish, Amoebic abscess Helminthic: Acute schisto Helminthic: Acute schisto

Case 29 y/o presents to urgent care with fever and myalgias for 3 days. He returned 4 days ago from a 3-week trip to Bangladesh. He is working for an NGO creating sustainable housing. Skin Exam Labs • WBC: 2.1 • HCT: 37 • PLT: 67 • Cr: 0.8 • AST: 78 • ALT: 93 • Alk Phos: 88 • Bili: 0.7

DDx and why? Dengue fever • 100 million infections/year • Mosquito vector (daytime) • Urban and rural

Dengue fever: worldwide distribution http://www.healthmap.org/dengue/en/ Dengue fever: clinical disease • Incubation period : Short (4-7 days) • Clinical Manifestations: – Fever, headache, joint and muscle aches – Nausea and vomiting – Rash • Labs : – leukopenia, thrombocytopenia, transaminitis • Dengue Hemorrhagic Fever/Shock – Occurs 3-7 days into illness, often w/ end of fever

Flushing Dengue rash 3-5 days erythema 1-2 days post onset of symptoms Morbilliform eruption w/ petechiae and islands of sparing Pincus LB. J Am Acad Dermatol. 2008 Phases of Dengue Infection Febrile phase Critical phase Recovery phase Potential clinical issues: ■ Shock ■ Bleeding ■ Organ impairment Viraemia IgG/ IgM Inf ammatory host response Capillary leakage 0 1 2 3 4 5 6 7 8 9 10 Time (days)

Dengue treatment/prevention • Risk for DHF -> high level of care • Treatment Capillary Leak Signs/Sx • Vomiting – Fluid resuscitation • Abdominal pain • ↑ hematocrit • Prevention • ↓ platelets • Effusions, ascites, bleeding – Insect avoidance – Vaccine – helpful in seropositive only Chikungunya fever • Came to Caribbean in 2013  C and S America – 1.7 million cases • 116 cases in US in 2018 • Still in Asia/Africa http://www.cdc.gov/chikungunya/geo/united-states.html

Chikungunya fever • Incubation period: 2-4 days (1-14) • Clinical manifestations (resolved within 7d) – Fever + Polyarthralgias 2-4 days later – Rash: ~ 50%, maculopapular • Labs : – Lymphopenia >> thrombocytopenia, transaminitis • Severe complications/deaths rare Chikungunya rash

Chikungunya: Diagnosis & Treatment • Lab diagnosis – IgM/IgG – PCR available • Treatment: – Supportive Zika virus • Incubation period: 2-4 days (1-14) • Clinical manifestations: – Fever, rash, joint pain, conjunctivitis – Severe complications rare: Guillian Barre • Risk of fetal complications greatest concern

Zika Paniz-Mondolfi et al. Clinical and Experimental Dermatology. 2018 Zika virus risk areas https://wwwnc.cdc.gov/travel/files/zika-areas-of-risk.pdf

Zika virus associated microcephaly • Recommendations to pregnant women – Avoid travel to Zika risk areas – Testing after travel to risk area • Considering pregnancy – Avoid for 2 months if woman visited – Avoid for 3 months if man visited https://www.cdc.gov/pregnancy/zika/testing-follow-up/exposure-testing-risks.html Zika vs. Dengue vs. Chikungunya

Case 63 year-old male with no PMH returned from a 10 day vacation to South Africa with complaints of fever, myalgias, and rash. Case continued 0 2 15 19 21 10 12 13 To US To South Africa In South Africa Fevers (Tm-101), myalgias, fatigue UCSF ED

Physical Exam • VS: 38.5, 76, 128/70, 16, 99% RA • Lymph: – 1 cm R inguinal LAD, mild tenderness • Skin: – right waistband region, 1.5 x 1 cm ulcer – 20 x small papulo-vesicular lesions Vitals: 38.5, 76, 128/70, 16

Labs and Microbiology Chemistry Hematology Chem 7 - wnl LFTS – wnl; UA - wnl \ / 3.8 -------- 214 Micro / 47 \ 7/18 - Bld Cx X 2 – NGTD 7/18 – thin/thick smear - neg African Tick Bite Fever • Rickettsia africae • Aggressive Bont ticks live on undulates and in grassy areas Mediannikov. Emerging Infectious Diseases 2010

Clinical Presentation • Fever • Headache • Muscle aches • Inoculation eschar, often multiple • Regional lymph node swelling • Rash – papular Jensenius M. African Tick Bite Fever . Lancet Infect Dis 2003; 3: 557–64. Rauolt D. Rickettsia Africae, A Tick- borne Pathogen In Travelers To Sub-Saharan Africa. N Engl J Med 2001, 344 (20) African tick-bite fever: skin findings