Travel Medicine: An Introduction to Common Diseases and Emerging Pathogens. Dr. Michael Payne Medical Microbiologist April 11 th, 2017

Transcription

1 Travel Medicine: An Introduction to Common Diseases and Emerging Pathogens Dr. Michael Payne Medical Microbiologist April 11 th, 2017

2 Faculty/Presenter Disclosure UBC Faculty: Michael Payne Relationships with commercial interests: Grants/Research Support: None Speakers Bureau/Honoraria: None Consulting Fees: None Other: Medical Microbiologist, Providence Health Care Consultant, Vancouver Coastal Health Travel Clinic

3 Outline Introduction to the field of travel medicine Overview of the most common infections found in returning Canadian Travellers Epidemiology, diagnosis, treatment and prevention of common travel related diseases Malaria Zika/Dengue/Chikungunya Yellow Fever Japanese Encephalitis Travellers Diarrhea Hepatitis A Typhoid Fever Meningococcal meningitis

4 Introduction to Travel Medicine Travel medicine is devoted to the health of travelers who visit foreign countries It is an interdisciplinary specialty concerned with: Prevention of infectious diseases during travel Personal safety of travelers Avoidance of environmental risks

5 r International Tourism is growing rapidly!

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7 r Canadians travel internationally often, 32.3 million in 2015, spending $29.4 billion US

8 Key Organizations

9 t Travel Vaccine Resources

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12 National Advisory Committee on Immunization (NACI) t

13 t BC Immunization Resource

14 Online Subscription Services t Teitelbaum P. (CATMAT) Travel medicine resources for Canadian practitioners. CCDR: Volume 41-05, May 7, 2015

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17 Overview of the most common infections found in returning Canadian Travelers

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19 No denominator data to guide absolute risk However, approximately, 20-70% of travellers will develop an illness while abroad/on return Adapted from Open Medicine 2014;8(1)e20

20 Common Travel Related Diseases

21 Case 1 A 40 year old male presents to a BC emergency room with a 5 day history of: fever abdominal pain headache He returned 10 days ago from 6 week trip to Ghana, where he was a supervisor at a mining operation

22 Investigations for Fever in Returning Traveller y CATMAT. Fever In The Returning International Traveller Initial Assessment Guidelines. 2011

23 Blood Smears Historically, collected using finger prick specimen (Is actually preferred specimen) Now typically use EDTA blood

24 Blood Smears y MMWR. June 3, 2005 / 54(SS02);39-40

25 Malaria Rapid Diagnostic Tests (RDT) RDTs are lateral flow immunochromatographic antigen-detection tests They detect malaria parasite antigens in blood Are rapid (15 minutes), and can be performed in areas without access to microscopy

26 Example t

27 Comparison of Methods t CATMAT. Canadian Recommendations for the Prevention and Treatment of Malaria

28 Patient Results y

29 Patient Results y Plasmodium falciparum, with a parasitemia of 3%

30 Parasitemia Calculated for all positive smears Is used to help estimate severity of disease, and response to therapy Having a parasitemia of 2% is associated with more severe disease

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32 Malaria 3.2 billion, 1/2 world's population is at risk ~ 214 million malaria cases occurred in 2015 ~ 438,000 malaria deaths occurred in 2015 About 90% of deaths occurred in Africa 66% of ALL deaths were in children <5 yo in Africa

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36 h Kiszewksi et al., American Journal of Tropical Medicine and Hygiene 70(5):

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39 From: Malaria in Travelers: A Review of the GeoSentinel Surveillance Network Clin Infect Dis. 2004;39(8): doi: / Date of download: 4/3/ by the Infectious Diseases Society of America

40 y Malaria is Decreasing!

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42 Malaria Treatment Back to the case! Our gentleman has a high parasitemia and is infected with the most severe species, P. falciparum Would need to be admitted and treated with intravenous artesunate

43 y Treatment Guidelines from The Medical Letter Vol. 11 (Suppl) 2013

44 Prevention On further history, our gentleman did not take malaria prophylaxis medicals, due to fear of side-effects Malaria prophylaxis drugs are ~95% effective Options are: Atovaquone-proguanil (Malarone) Doxycycline Chloroquine Mefloquine

45 Prevention Also important to use other prevention methods, such as: Insecticide treated bed nets DEET 30% or Picaridin 20% Wear clothing that covers as much skin as possible Avoid activities between dusk and dawn

46 Case 2 A 25 year old woman presents to the ER, returning from a trip Costa Rica 3 days ago She describes a 5 day history of: Fever Headache Rash Generalized muscle and joint pain

47 Further History She was there for 2 weeks She remained in city of San Jose, but reports receiving many mosquito bites No other exposures (Food, freshwater, new sexual contacts)

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49 Arboviruses Zika, dengue and chikungunya are all spread by Aedes aegypti and A. albopictus mosquitoes They cause a similar clinical syndrome Their geographic range has been rapidly expanding over the past decade

50 t Zika Outbreak

51 Recent cases in Miami and Texas Main concerns are microcephaly and Guillain-Barré syndrome

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53 r Zika in Latin America

54 Dengue Breakbone Fever million people are infected each year approximately 3.2 million severe cases and 9000 deaths The dengue virus (DEN) comprises four distinct serotypes If you have infection with one type you are more susceptible to severe disease if infection with a different serotype

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56 Chikungunya An alphavirus, first described in Tanzania in 1952, "that which bends up Has spread in range, with an outbreak in Latin America in causing millions of cases

57 Diagnosis For all viruses, PCR from blood is most useful in first 7 days, after this time, serology is used However, for Zika and Dengue, cross reaction of serology is a problem with other flaviviruses: Yellow Fever Japanese encephalitis West Nile virus

58 Diagnosis of Zika

59 Back to the Case As the patient had 5 days of symptoms, PCR of blood was sent positive for Zika virus The patient is married (Husband travelled with her) Wondering how long to wait before attempting to get pregnant

60 CDC now recommends all men with possible Zika virus exposure who are considering attempting conception wait at least 6 months after symptom onset (if symptomatic) or last possible Zika virus exposure (if asymptomatic) Women with possible Zika virus exposure are recommended to wait at least 8 weeks after symptom onset (if symptomatic) or last possible Zika virus exposure (if asymptomatic) before attempting to get pregnant.

61 NONE Treatment

62 Prevention Daytime mosquito precautions with 30% DEET or 20% picaridin Limit mosquito populations: Pesticide spraying Elimination of breeding sites Don t travel to anywhere fun

63 Vaccines CYD-TDV/Dengvaxia is a quadravalent Dengue vaccine, which was recently endorsed by the WHO and licensed in multiple countries Has not been evaluated for travellers Zika vaccine research is ongoing, with clinical trials in progress

64 Case 3 A 22 year old medical student is travelling overseas for a 2 month clinic placement in both Kampala, Uganda and Nairobi, Kenya They are wondering about Yellow Fever vaccination as their university said it would be needed for entry

65 Yellow Fever Is a flavivirus spread by Aedes spp. and Haemagogus spp. mosquitoes It causes fever, hepatitis and in severe cases, hemorrhage For a 2-week stay, the estimated risks for illness due to yellow fever for an unvaccinated traveler visiting an endemic area is: West Africa are 50 per 100,000 South America are 5 per 100,000

66 Yellow fever risk areas

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68 Prevention Yellow fever vaccination is recommended for travellers to risk areas In addition, it is REQUIRED by many countries, if the traveller is coming from a YF endemic country Therefore, certificates are issued to prove vaccination status Vaccine, is a live strain of YF, and can rarely cause severe reactions Highest risk in age <9 months and >60 years

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70 Case 3 Given risk of disease, and the fact that Kenya would require proof of vaccination Patient was vaccinated for YF, with certificate given

71 Case 4 A 24 year old male is travelling with 3 friends through SE Asia for 3 weeks, in April They have an open itinerary, but will visit: Vietnam Laos Thailand Bali Cambodia They will be staying mostly in cities and resorts They have read about Japanese encephalitis virus, and want to know if getting the vaccine is needed

72 Japanese encephalitis virus (JEV) JEV is a single-stranded RNA virus that belongs to the genus Flavivirus JEV virus is transmitted by Culex species The virus is maintained in an enzootic cycle between mosquitoes and primarily pigs and wading birds

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74 Japanese encephalitis virus (JEV) Most people infected will not become ill, (1/25-1/1000) If develop symptoms 20-30% will die Of survivors, 30-50% will have longterm neurological or psychological sequelae Incidence in susceptible populations in endemic areas is ~5-50 cases/100,000 children/year

75 Japanese encephalitis virus (JEV) Risk in travellers is low! From , 68 JEV cases among travelers were published or reported to CDC 2 cases were reported in a large GeoSentinel review (1 Cambodia, 1 Thailand) Ann Intern Med March 19; 158(6):

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77 Japanese encephalitis virus (JEV) New vaccine for JEV (Ixiaro) was approved in 2011 Inactivated vero cell culture-derived 2 doses at 0 and 28 days Accelerated series at 0 and 7 days has also been studied Little data on effectiveness, but after 2 doses, 96% of adults and 100% of children developed protective neutralizing antibodies Journal of Travel Medicine 2015; Volume 22 (Issue 4):

78 Japanese encephalitis virus (JEV) Booster dose (3 rd dose), if at continued risk, should be given at 1 year Subsequent study has show protection likely last for 10 years after 1 st booster dose Vaccine is very $$$$$ Cost is $200/dose

79 JEV Key Messages Risk to traveller is low, consider if: Travel during high transmission season (Summer to fall) Long term stay (Longer than 30 days in rural areas) Consider in shorter stays if spending time outdoors at night Active JEV outbreak occurring Risk needs to be balanced with cost, can also use mosquito avoidance techniques CATMAT, Japanese Encephalitis, 2011.

80 Case 4 Patient is travelling for less than 30 days and will be in mainly urban areas Therefore, vaccination not given

81 Case 5 A 18 year old student returned from a month long trip to India 10 days ago He was staying with family in Chandigarh He presents with a 2 day history of fever, abdominal pain and headache

82 Typhoid Fever Typhoid fever is caused by Salmonella Typhi (Salmonella Paratyphi), through ingestion of contaminated food or water 10% case fatality rate (untreated, low income countries), this is <1% with appropriate treatment in high income countries 2-5% of people can become asymptomatic chronic carriers The acute illness is characterized by: prolonged fever, headache, nausea, loss of appetite, and constipation or sometimes diarrhea Incubation period is typically 8-14 days Canadian Immunization Guide. Typhoid Vaccine

83 Typhoid Fever 21 million cases worldwide annually, with 222,000 deaths Was the most common vaccine preventable disease in GeoSentinel database (2010) Approximately, 117 cases per year in Canada Diagnosed by blood, stool or urine cultures

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85 Risk to Traveller The estimated risk of developing travel associated typhoid is about: 1/3,000 travellers for travel to the South Asia 1/50, ,000 for travel to Sub-Saharan Africa, North Africa and the Middle East, or South America < 1/300,000 for travel to the Caribbean and Central America Risk of infection/severe disease increased if: Anatomical and functional asplenia Children Duration of travel (>2 weeks) Visiting friends or relatives Achlorhydria or use of acid suppression therapy HIV or other immunocompromised patients CATMAT, Typhoid Fever.

86 Treatment Treatment is with ceftriaxone or ciprofloxacin for 7-14 days Our case is treated with ceftriaxone for 14 days On further history the patient has a summer job in a restaurant Need to ensure three negative stools before returning to work Healthcare workers Daycare workers/attendees Food handlers

87 Vaccine There are 3 vaccine types available for S. Typhi in Canada: Salmonella Typhi Vi capsular polysaccharide vaccine for injection (Typh-P) Protection for 3 years Typh-P combined with hepatitis A Live, oral, attenuated TY21A typhoid vaccine (Typh-O) Protection for 7 years Efficacy of all vaccines is ~50-60% for preventing Typhoid disease Some cross protection for S. Paratyphi (Typh-O only) Canadian Immunization Guide, Typhoid Vaccine.

88 Vaccine CATMAT recommends using the typhoid vaccine where risk to traveller exceeds 1 in 10,000 Therefore, only travellers to South Asia would qualify (Afghanistan, Bangladesh, Bhutan, India, Maldives, Nepal, Pakistan and Sri Lanka) For other destinations consider if: Children visiting friends and relatives longer duration of travel (>2 weeks) achlorhydria or use of acid suppression therapy Patient preference

89 Key Messages Typhoid fever is a serious illness, with 68-90% of cases in returning travellers requiring hospitalization Indicated to for travellers to South Asia, perform risk assessment for other travellers Both Typh-P and Typh-O provide 50-60% protection Typh-O has a longer duration of protection, but must be balanced with increased adverse events, cost and contraindications

90 Case 6 34 year old male seen in the ER on March 12th with travel to Mexico from February 21 st to 29 th Developed fever/chills, abdominal pain 15 days after return Bloodwork Showed ALT 6500 AST 2500 He was jaundiced on clinical examination

91 Hepatitis A RNA virus of the Picornaviridae family, genus Hepatovirus Causes acute hepatitis, and is transmitted by the fecal-oral route Long incubation period (15-50 days) For young children (<6 years old), most infections are asymptomatic or mild Older children and adults typically have symptoms, some groups are at higher risk of severe hepatitis: Immunocompromised patients Chronic liver disease Elderly

92 Risk to Travellers In a GeoSentinel review from , there were 120 cases of acute hepatitis A Pre-travel visit for 18.3% of cases Ann Intern Med March 19; 158(6): Vaccine 28 (2010)

93 Is no where safe??? 282 cases of HAV in Hawaii

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95 Diagnosis Serology for hepatitis A IgM and IgG detect acute infection and immunity, respectively Out case was positive for IgM only He recovered fully Family contacts need to be followed up with/vaccinated He was not a health care work, food handler or a day care staff

96 Vaccine Inactive vaccine, given at 0 and 6-12 months Due to long incubation, can be given up to the day of travel When used for pre-exposure, HA vaccine is 90-97% effective in preventing clinical disease Canadian Immunization Guide. Hepatitis A Vaccine.

97 Recommendations In BC, publically funded for individuals with: Hemophilia A or B Chronic liver disease HIV HSCT MSM Illicit drug use Inmates Close contacts of hepatitis A case Recommended, not free for: Food handlers Travellers

98 Duration of Protection Protection from a 2 dose schedule likely lasts from 20 years, to life Therefore, routine booster doses are not recommended at this time in Canada Canadian Immunization Guide. Hepatitis A Vaccine.

99 Case7 A 22 year old male returned 3 weeks ago from a 7 day trip to Puerto Vallarta He had an episode of acute diarrhea on day 3 of his trip, which improved after 1 day He continues to have abdominal upset and intermittent diarrhea

100 Illness Course Traveller s Diarrhea usually presents within 3 to 4 days of travel Symptoms typically last 3-4 days Incapacitating symptoms typically only last up to 1 day (12-50% of patients) A health care visit occurs for 10-20% of travellers 30-60% take medication CATMAT Statement on Travellers Diarrhea, 2015.

101 Duration of Symptoms Most patients have resolution in 3-4 days If last longer than 2 weeks is categorized as chronic diarrhea (2-10%) JAMA, March 4, Vol 249, No 9.

102 GI illness was the diagnosis in 45% of returning ill travelers! t MMWR / July 19, 2013 / Vol. 62 / No. 3

103 Risk by Region g JAMA January 6, 2015 Volume 313, Number 1

104 Risk by Types of Travel Highest risk travellers are those on vacation Business travel is less risky Luxury accommodations are not necessarily protective Backpackers and adventure travelling has been associated with higher rates of TD Summer travel and high rainfall increase risk Cruise ship passengers have lower risk of TD However, are at greater risk of large gastro-enteritis outbreaks Eur J Epidemiol Mar;5(1): JAMA, March 4, Vol 249, No 9.

105 Age Differences Older patients (>60 years old) are less likely to suffer from acute TD J Travel Med 2012; 19:

106 Common Pathogens t Am. J. Trop. Med. Hyg., 80(4), 2009, pp

107 Diagnosis Diagnosis t BCGuidelines.ca (Infectious Diarrhea)

108 Case 7 Stool culture, ova and parasite were negative Patient was diagnosed with post-infectious irritable bowel syndrome His symptoms slowly improved over a 1 month period

109 Prevention boil it, cook it, peel it, or forget it makes biological sense but little data supports its use Review in 2005 examined 8 studies, of which 7 showed no correlation between types of food selected and risk of TD Very few travellers actually adhere to these recommendations Other Preventive Methods Preparing your own food is protective Water Purification methods Hand washing Probiotics Prevention of Traveler s Diarrhea, CID 2005:41 (Suppl 8).

110 Vaccination Oral Cholera Vaccine (Killed whole cells plus recombinant B-subunit (WC-rBS) There is only 1 licensed vaccine in Canada for prevention of Cholera and TD, Dukoral It is composed of: Heat inactivated V. cholerae O1 Inaba classic strain Formalin inactivated V. cholerae O1 Inaba El Tor strain Heat and formalin inactivated V. cholerae O1 Ogawa classic strain Recombinant non-toxic cholera toxin B subunit Efficacy is about 86% for epidemic cholera and approximately 25% for overall travellers' diarrhea Protection for Enterotoxigenic Escherichia coli (ETEC) lasts 3 months PHAC. National Advisory Committee on Immunization (NACI).

111 Treatment First line treatment is loperamide Immodium Antibiotics are reserved for severe disease Ciprofloxacin/azithromycin

112 Colonization with Multi-drug resistant (MDR) Bacteria MDR Enterobacteriaceae are resistant to 3 rd generation cephalosporins (ESBL) +/- carbapenems (CRE) Limited options are available for their treatment Previously, a major risk factor was receiving health care overseas Now have evidence that any travel to developing countries may place patients at higher risk of acquisition

113 Risk of Acquisition of MDR Bacteria t Antimicrobials Predispose to ESBL-PE, CID 2015:60 (15 March).

114 Risk of Acquisition of MDR Bacteria Loperamide alone not associated with increased risk Highest risk loperamide plus an antibiotic EID. Vol. 22, No. 1, January 2016

115 Outcomes of Travellers Diarrhea TD is associated with important secondary illnesses: Guilliane Barré syndrome Reactive arthritis Post infectious irritable bowel syndrome (IBS) Chronic diarrhea J Travel Med 2013; 20: Aliment Pharmacol Ther 2015; 41:

116 Case 8 A 21 year old university student is volunteering for an NGO, building schools, for 1 month in Nigeria Her trip departs on January 15 th and she is wondering if she needs the meningococcal vaccine

117 Meningococcal Meningitis Meningococcal disease is caused by Neisseria meningitidis The five major serogroups most commonly associated with invasive disease are A, B, C, Y and W135 Serogroup B and C most common in Canada

118 t NACI. Advice for the use of the Multicomponent Meningococcal Serogroup B (4CMenB) Vaccine, 2014.

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122 Meningococcal Meningitis Vaccines Monovalent conjugate meningococcal vaccines (Men-C-C) Quadrivalent conjugate meningococcal vaccines (Men-C-ACYW) Menactra (meningococcal groups A, C, Y, and W-135 polysaccharides conjugated to diphtheria toxoid protein) Menveo (meningococcal groups A, C, Y and W-135 oligosaccharides conjugated to CRM197 protein) Multicomponent meningococcal vaccine (4CMenB) Bexsero (meningococcal porin A [PorA], factor H binding protein [fhbp], neisserial antigen 2091 [GNA2091], heparin binding antigen [NHBA], neisserial antigen 1030 [GNA1030], and Neisserial adhesion A [NadA] surface proteins)

123 Meningococcal meningitis Travellers to the Hajj and Umrah pilgrimages Large outbreaks of W-135 in 2000, 2001 Required (Saudi Arabia) quadrivalent conjugate vaccination(a,c,y,w-135) 10 days before arrival and within the last 3 years, need certificate All travellers 2 years and older MenB not required, unless active outbreak occurring

124 Meningococcal meningitis Is recommended for travellers to the African meningitis belt Particularly during high transmission season (Dec to June) Can be considered if traveller is going to be a student, living in confined areas Not needed for clinicians Needed for laboratory works Travellers do not need to receive 4CMenB vaccine unless there is evidence of an outbreak that is known to be caused by serogroup B that can be prevented by the vaccine CATMAT. Statement on Meningococcal Disease and the International Traveller

125 4CMenB Use in BC and Canada still being determined 66% of the overall proportion of Canadian serogroup B meningococcal strains are predicted to be susceptible to the 4CMenB vaccine N Engl J Med 2016;375:220-8.

126 Case 8 Given patient is travelling for a month, during the dry season, quadravalent vaccine was given

127 Outline Introduction to the field of travel medicine Overview of the most common infections found in returning Canadian travelers Epidemiology, diagnosis, treatment and prevention of common travel related diseases Malaria Zika/Dengue/Chikungunya Yellow Fever Japanese Encephalitis Travellers Diarrhea Hepatitis A Typhoid Fever Meningococcal meningitis

128 The End Thanks! Questions?