Travel: Chikungunya, Zika,.. New worries McGill Family Physician Refresher Course Dec 6, 2016 Makeda Semret, MD FRCP(C) Infectious Diseases/ Medical Microbiology
Disclosures Funding from PHAC/CIHR/GSK/Novartis for influenza surveillance in Montreal In-kind research support from biomerieux for work on Hospital-Associated Infections in Africa (Ethiopia) No speaking or consultancy fees from industry 2
Objectives Know when to suspect an arboviral (arthropod-borne virus) infection in travelers and common clinical scenarios Know what laboratory tests to send and the limitations of these tests Know current guidelines for management of Zika exposure, and available resources 3
37 year old female, previously healthy Presents to your clinic with fever, myalgias, malaise, lethargy x 3 days. Returned 12 days ago from one week stay in Haiti No localising signs and symptoms Temp 38.2 0 C, BP 120/80, HR 108, RR 20 Looks unwell but not toxic Cardiac, Resp, Abdo, MSK: unremarkable WBC 3.0 (lymphs 1.0); Plt 95; Hb 122 4
Your working diagnosis? Further investigations? Further management? 5
Fever from the tropics leading life-threatening illness The No. 1 life threatening infection for travelers about 30,000 European and N. American travelers infected annually,?150 die 4% mortality (P.f.); 20% in severe cases Am J Trop Med Hyg 2013;88:397 404. 6
Malaria in travellers leading life-threatening illness Am J Trop Med Hyg 2013;88:397 404. 7
First Key Message In a febrile patient from the tropics, always rule out malaria (and bacterial sepsis) - TODAY. You cannot (in Canada) make a firm diagnosis of an arboviral infection on the first visit. 8
Second Key Message: Geography! Ann Intern Med. 2013;158:456-468 9
Third message: things change!! Chikungunya Dec 2013 Chikungunya Dec 2014 10
Things change.. 11
Why do (did) these diseases spread? Some of these viruses can be transmitted human to human but not a preferred route, and therefore relatively low risk E.g., sexual transmission of Zika virus Spread of these diseases follow the distribution of the vector (the mosquitoe) Distribution influenced by climactic changes and vector adaptation 12
Vectors for Transmission for Dengue, Chikungunya, Zika: Aedes sp Day feeders; once infected, mosquitoes stay infected for life (30-45d) Also responsible for Yellow Fever transmission! Aedes aegyptii Aedes albopictus 13
Adaptation of the vector Slide courtesy of Dr M. Libman
Societal changes: uncontrolled urbanization Slide courtesy of M. Libman
World Wide Distribution of Aedes aegypti elife 2015;4:e08347, accessed Nov 19, 2016 16
The viruses Dengue and Zika are flaviviruses Same family as Yellow Fever, West Nile, Japanese encephalitis They can cross-react in serological tests (! vaccinees) Chikungunya is an alphavirus Same family as Mayaro, O'nyong'nyong, and others associated with encephalitis, arthritis syndromes No serological cross-reactions with dengue or zika 17
They initially present in much the same way Short Incubation (3-10d most frequently) Fever, myalgias, headache, malaise +/- rash: last 3-7 days Low WBC and Plts How do you differentiate? 18
First, worry about Dengue Frequent cause of fever in travelers from SE Asia and Central America/Caribbean. Can lead to severe illness with possible hemorrhagic fever (rare) --- you can't tell who will progress to severe disease until a good 72h after defervescence Monitor closely for warning signs 19
Warning signs Abdominal pain or tenderness Persistent vomiting Clinical fluid accumulation (ascites, effusions) Mucosal bleeding Lethargy/restlessness Liver enlargement > 2cm Hematocrit increase, rapid decrease in PLT Start at defervescence (D5-6) and last 48-72h 20
Manage (while waiting for diagnosis) Supportive treat symptoms but avoid NSAIDS if dengue still a possibility potential for bleeding Testing: serology (requesting serology for all 3 makes sense, but in practice dengue +/- chik first) Follow-up (at least by telephone) to ensure no progression If dengue: no long-term sequelae; also no life long immunity (at least 4 different serotypes) - so discuss risk of re-infection 21
Chikungunya "to walk bent up in makonde - nothing to do with chickens! Initial presentation like dengue More arthralgias/arthritis but often these occur later (after defervescence) - can lead to significant morbidity, other complications rare Immunity after infection is probably lifelong 22
Back to our patient Improves with symptomatic management A few days later tells you she has been trying to get pregnant She has no joint symptoms You are still waiting for her serology results.. 23
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Zika beware what you think you know http://www.vox.com/2016/2/19/11062000/zika-virus-unknowns-questions 25
Zika beware what you think you know http://www.cdc.gov/zika/geo/active-countries.html accessed Oct 15 2016 26
Zika Infection typical clinical disease Incubation usually 2 to 14 days Resolves spontaneously Approx 80% asymptomatic http://www.goinvo.com/features/zika/
Zika Infection vertical transmission Vertical transmission Est. Risk of microcephaly from Zika infection in T1 = 1-13% First time we face infectious epidemic teratogen since rubella Neither pre-2007 Asian nor African lineages directly implicated with congenital Zika syndrome or neurologic illness (unnoticed vs different bio?) http://www.goinvo.com/features/zika/
Zika Infection sexual transmission Human cases Confirmed in 9 nonendemic countries and 3 endemic countries High endemic F:M ratio suggests it s common Vaginal, oral, anal sex Mostly M F even without symptoms RNA persistance Fluid Typical Record Blood* 7-14d * 81d* Urine 14 Saliva? (no known transm) Semen? 188d (culture -) Vaginal secretions? 14 Breats milk (only 1 case of live virus, no transm reported)?? 69d (culture +) http://www.goinvo.com/features/zika/
Precautions/prevention for zika? Since many infections are asymptomatic : travellers to endemic area and who want to eventually conceive should have protected sex (or abstain) for: 6 months for Men; 2 months for Women (CDC and PHAC) 6 months for both (WHO) Barrier precautions for duration of pregnancy if already pregnant http://healthycanadians.gc.ca/diseases-conditions-maladiesaffections/disease-maladie/zika-virus/prevention-eng.php ttps://www.cdc.gov/zika/prevention/protect-yourself-during-sex.html http://www.who.int/csr/disease/zika/information-for-travelers/en 30
Who to test? Any pregnant woman who has been in an area with Zika: If symptomatic and within 14 days of symptoms send both PCR of blood+urine AND serology If no symptoms (or > 14 days since symptoms): send serology (PRNT will be done if IgM positive) If >12 weeks since trip or symptoms, do not send (false negatives), but recommend to follow ultrasound Ultrasound within 4 weeks of exposure and q 4 weeks until lab results 31
Important details on testing Testing will be rejected by provincial lab unless details of travel (dates, place) and symptoms (with dates) are provided legibly on the requisition. You can test Men if specify "wishing to conceive, pregnant partner, adding epidemiological info (area, dates of travel) 32
Zika in Canada As of 30 Sept 2016: 328 travel associated cases 2 sexually transmitted cases 2 maternal fetal transmissions 14 pregnant women Outcome available for 2 only one with Zika associated abnormalities, one without 33
Counselling for our patient What would you advise her pending results? What would you advise if she had been asymptomatic? What if her Zika serology comes back negative? And if her partner had traveled with her? And if he had not traveled with her? 34
Many unanswered questions True risk of vertical transmission? By trimester? % of vertical transmission with clinical consequences? Importance of sexual transmission, and max duration of infectivity? Neurological complication rate for adults? Clinical differences between lineages? 35
Take home messages Don t forget malaria commonest life threatening cause of fever. Arboviruses are more frequent causes of fever in travelers from the Americas and SE Asia. Most are self limited Dengue can sometimes be life threatening Chikungunya can lead to chronic morbidity Zika is an issue for pregnancy 36
Take home messages (cont d) The results of tests for all these diseases take several weeks to become available; also issue of cross reactivity, so clinical and epidemiologic context is important PREVENTION: No vaccines for any! Day-biting mosquito-avoidance (DEET/ICARDIDIN; light-coloured clothing, wind, air conditioning) 37
Questions? J.D. MacLean Centre for Tropical Diseases https://www.mcgill.ca/tropmed/ Makeda.semret@mcgill.ca 38