Evaluation of Fever in the Returning Traveler

1. Evaluation of Fever in the Returning Traveler Denise Watt November 26, 2009

2. Objectives • Approach to the febrile traveler • History • Travel history • Immunization history • Chemoprophylaxis • Investigations • Treatment • Brief overview of the most commonly imported diseases

3. Background • >500,000,000 people cross international boundaries each year • >12,000,000 North Americans travel to developing countries each year •  international travel =  importation of exotic infectious diseases Suh, K, et al. Evaluation of Fever in the Returned Traveler. Medical Clinics of North America 1999:83(4)997-1018.

4. Travelers get sick …. • 20-70% of travelers report health problems while traveling • 1-5% seek medical attention abroad • 0.01-0.1% require emergency medical evacuation • 1 in 100,000 dies Kain K, Ryan E. Health Advice and Immunization for Travelers. NEJM 2000;342(23)1716-1725.

5. Low awareness of traveler’s health issues • Many travelers do not seek predeparture medical consultation • Poor understanding of risks • Not covered by health insurance • Shortage of physicians with travel medicine expertise

6. For example … • Study of 353 North American passengers boarding international flights to regions where Hepatitis A is endemic • 72% did not obtain immunizations • 78% did not know the route of transmission of hepatitis A • 95% unable to identify fever, abdominal pain, jaundice as symptoms • 88% of flight crew were not immunized • Quoted in: Thanassi M, Thanassi W. EMR 1998;9(22)239-246

7. The result …. • 1-2% of unimmunized travelers visiting a developing country for >1 month will develop hepatitis A • Steffen R. Risk of hepatitis A in travelers: the European experience. Journal of Infectious Disease 1995;171:S24-28. • 300 / 100,000 travelers / month in tourist areas of developing countries • 5-7 x increased risk for “backpackers” • Quoted in:Kain K, Ryan E. Health Advice and Immunization for Travelers. NEJM 2000;342(23)1716-1725.

8. After the holiday … • Swiss study • 4% of travelers to developing countries for >3 weeks develop fever • 61-71% remained febrile upon return Steffen R, et al. Health problems after travel to developing countries. J Infect Dis 1987;156:84-91. • 5% of travelers consult MD upon return Thanassi M, Thanassi W. EMR 1998;9(22)239-246

9. Many of the returning ill will present to the Emergency Department

10. ED evaluation of the febrile traveler • What infections are possible given the patient’s travel history • What infections are probable given the patient’s medical history and presentation • What infections are life-threatening or contagious or both

11. General Medical History • Immunocompromise • Increased risk of all infectious diseases • Decreased gastric acidity (achlorhydria, H2 blockers, PPI) • Increased risk of enteric illness (eg: cholera, typhoid) • Chronic respiratory disease • Increased risk of respiratory infections

12. Asplenia • Encapsulated organisms • Sickle Cell Trait / G6PD deficiency • Confer protection against malaria

13. Pre-travel History • ? pre-departure medical consultation • Vaccination status • Which vaccines • When • Chemoprophylaxis • Which specific medication • Dosing schedule • Patient compliance

14. Travel Immunizations

15. Vaccination against the following makes diagnosis unlikely: • Yellow fever • Hepatitis A • Hepatitis B • Vaccinations for following are not very effective • Typhoid • Cholera

16. Travel History • Precise dates of travel • Arrival & departure from endemic regions • Countries and regions visited • Urban • Rural • Type of accommodation •  hotel • Bamboo hut

17. Infection prophylaxis • Insect repellants • Mosquito nets • Bottled water • Activities • Freshwater exposure (rafting, swimming...) • Trekking • Contact with animals • Drug use

18. Sexual contacts • 66% of 213 Australians going to Thailand reported plans to have sex • 25% of Swedish women on charter holidays reported a sexual encounter with an unknown partner • 18.6% of 757 patients at Hospital for Tropical Diseases in London reported new sexual partner during last trip • Only 36% regularly used condoms Quoted in: Matteelli A, Carosi G. Sexually Transmitted Diseases in Travelers. Clinical Infectious Diseases 2001;32:1063-1067.

19. Physical Exam • Jaundice • rash • lymphadenopathy • Hepatosplenomegaly • Altered LOC • hemorrhage

20. Investigations • CBC • Renal function, U/A • LFTs • Malaria thick and thin smears • Serology • Stool C+S, O+P • Blood C+S • LP

21. Commonest causes of fever (%) sources: O’Brien D, et al.Clinical Infectious Diseases 2001;33:603-9. Suh, K, et al. Medical Clinics of North America 1999:83(4)997-1018.

22. Incubation Periods • Short (<1 week) • GI bacterial pathogens • Dengue Fever • Yellow Fever • Medium (1-2 weeks) • Malaria (falciparum) • Typhoid • Trypanosomiasis • Q fever

23. Incubation Periods • Long (>3 weeks) • Viral hepatitis • Malaria (vivax, ovale, malariae) • Schistosomiasis • Tuberculosis • Amoebic liver abscess • TB

24. Case 1 • 35 y.o. oilfield worker in rural Sudan • Returned 5 days ago after 6 months abroad • Fever, chills, cough started yesterday • What else do you need to know?

25. PMHx Healthy Pre-departure consultation by GP Vaccinated against HAV/HBV, Typhoid Prescribed mefloquine for malaria prophylaxis. Stopped taking it because of concerns of long term side-effects

26. Physical 105 14 110/75 39.80 Diaphoretic Otherwise normal examination CXR Normal Laboratory Hb 110 WBC 8 Platelets 65 Lytes normal Malaria smear negative

27. What is your differential diagnosis? • What is the most dangerous likely pathogen? • How would you manage this patient?

28. Malaria Merozoite of p. falciparum

29. Malaria, what is it? • Protozoal infection caused by • Plasmodium falciparum • Africa, East Asia, Oceania, Haiti • 50% of all cases • 95% of all deaths • Plasmodium vivax • Central America, Middle East, India, SE Asia • Plasmodium ovale • Plasmodium malariae • NB: Mixed infections common

30. Malariathe vector Anopheles mosquito • Also maternal-fetal, blood transfusions, dirty needles, etc.

31. Malaria life-cycle

32. MalariaEpidemiology • >2 billion people (41% of the world population) live in malaria-risk areas • Endemic to >100 countries • Every year • 300-500 million people get malaria • 1.5-2.7 million people die from malaria • 90% in rural, sub-Saharan Africa • Disproportionately in children <5

33. Malaria in Canada • 1994 – 430 cases reported • 1995 – 621 cases reported • 1997 – 1036 cases reported • Per capita rate 10x as high as USA • 1994-1997 – tenfold increase in severe malaria requiring admission to ICU • Calgary has among the highest per capita rate in Canada (oil & gas industry) Kain K, et al. Malaria deaths in visitors to Canada and in Canadian travellers; a case series. CMAJ 2001;164(5)656-659

34. Malaria

35. Malaria Symptoms Headache Muscle aches Diarrhea Fever Chills Vomiting Coughing Abdominal pain Malaria symptoms usually appear within 7 to 21 days of the mosquito bite, but may not appear until later

36. Interval between date of entry and onset of illness by plasmodium species for imported malaria cases in the United States (1992) Adapted from MMWR 44:1-14, 1995

37. Malaria is …. • Usually preventable • Almost always curable Nobody should die of malaria!

38. Early diagnosis and treatment of malaria is crucial to preventing morbidity and mortality • 40% of malaria mortality in US is due to missed diagnosis • Stanley J. Malaria. Emergency Medicine Clinics of North America • 1997;15(1)113-155.

39. Plasmodium Falciparum Two merozoites of Plasmodium falciparum (blue and pink) in red blood cell

40. Plasmodium Falciparum • Potentially fatal due to: • Expression of membrane proteins causing adherence of red cells to endothelial walls • End organ microcirculatory occlusion and tissue ischemia • Death usually due to brain or lung injury • Other species rarely fatal as they do not induce cytoadherence

41. Plasmodium Falciparum Malaria • Renal failure • Hepatic failure • Pulmonary Edema • Seizures • Coma • Death (up to 7% of North American and European travelers) • Lobel HO, Kozansky PE. Update on prevention of malaria for travelers. JAMA. 1997; 278(21): 1767-1771.

42. Back to our case… • You correctly have malaria on the top of your differential diagnosis • What investigations rule in or out malaria

43. MalariaDiagnosis • Current Standard of Care • Thick film – screen for malaria • Thin film – species identification • Gold Standard • PCR • detect low levels of parasitemia and mixed infections • The Future • Dipsticks – presently being investigated

44. MalariaDiagnosis • Thick/Thin films often negative with low levels of parasitemia • A high index of suspicion requires repeat films q12h x 3 to rule out malaria

45. Our patient’s thin smear shows malaria of undetermined species? • Is this a severe or uncomplicated infection? • What are you going to treat it with? • What if the initial smear is negative? • Are you going to treat?

46. MalariaTreatment • Choice of treatment based on • Species of malaria • Level of parasitemia • Likelihood of drug resistance • Severity of infection

47. Malarialaboratory investigations • All of the following are necessary to determine severity of disease • CBC • LFTs, bilirubin • INR, PTT • BUN, Creatinine • Glucose • Urinalysis

48. Criteria for severe P.falciparum Either • Asexual forms of Plasmodium falciparum on blood smear Or • History of recent possible exposure and no other recognized pathology

49. And 1 or more of: • Decreased LOC • Severe normocytic anemia • Renal failure • Pulmonary edema • Hypoglycemia • Shock • Spontaneous bleeding / DIC • Seizures • Acidosis • Hemaglobinuria • >5% parasitemia in non-immune individuals

50. Malariadrug resistance Kain, K et al. Malaria deaths in visitors to Canada and in Canadian travellers. CMAJ (2001);164(5)654-9