Thread by @BoggildLab

❗️Just what you’ve been waiting for❗️Sunday @BoggildLab #Tweetorial on Fever in the Returning Traveler!! 🤒✈️🏝🏖💉🦟🌞Buckle up, friends 😊🙏🙏 @MedTweetorials @AcademicChatter #AcademicChatter #MedTweetorials #Fever #Travel #VectorBorneDisease #VaccinesWork 1/23

2/23 Fever = hypothalamic thermostat reset to a ⬆️ temp in response to infection. It’s an adaptive biological response to pathogen invasion that assists w/ immunological control of infections. Most texts refer to fever as temp >38 C. See JAMA paper also: ncbi.nlm.nih.gov/pubmed/1302471

3/23 Fever in returning travelers is common in our population due to high mobility & travel proclivities. We collectively log millions of miles of air and land transit annually to countries that have very different endemicity profiles for infectious diseases compared to 🇨🇦 or 🇺🇸

4/23 Fever in traveler to tropics = medical emergency & malaria until proven otherwise. B/c fever can = serious infections of public health significance, its presence post-travel warrants prompt medical eval. For topic overview, see latest Mandell's post-travel iillness chapter.

5/23 Our @PHAC_GC CATMAT guidelines in 🇨🇦 provide a step-wise algorithmic approach to fever in the returning traveler, which is rooted in epidemiology & concept that destination is a critical correlate of diagnosis. National guidelines can be found at: canada.ca/content/dam/ph…

6/23 Our @PHAC_GC CATMAT guidelines ask clinicians to consider several influencers of DDx of fever in returning travelers incl. exposure history, fever duration & pattern. Eg, freshwater exposure + fever duration <21 days + "saddleback" pattern all support DDx of leptospirosis.

7/23 Destination = key influencer of DDx as per 🇨🇦 guidelines. Most malaria in febrile returned travelers is imported from W Africa, while most dengue comes from Asia & Americas. See classic @_ISTM_ @GeoSentinel paper by super⭐️ mentor Dr. Mary Wilson: ncbi.nlm.nih.gov/pubmed/17516399

8/23 If we restrict analyses to returned travelers from W Africa, as we did for our @AnnalsofIM paper, we see that malaria plays an even more prominent role in the DDx, accounting for 40% of travelers returning with fever. ncbi.nlm.nih.gov/pmc/articles/P…

9/23 Interval to presentation of fever post-travel = proxy for incubation period. In this classic figure from the @GeoSentinel fever paper, we demonstrate that most falciparum malaria presents w/in 30d, while most vivax malaria presents >30d post-travel. ncbi.nlm.nih.gov/pubmed/17516399

10/23 In single- & multi-centre studies, malaria is the most common specific cause of fever in sick travelers returning from the tropics, followed by the febrile gastroenteritides, respiratory tract infections & dengue. Rounding out top 5 is usually enteric fever (typhoid)

11/23 This DDx generally holds across studies & over time, except in outbreaks. See DDx from our @PHAC_GC guidelines alongside our CanTravNet analysis of Chikungunya. Prior to Chikv outbreak in Americas, dengue outnumbered Chikv imports by 10:1. Ratio equalized during outbreak.

12/23 In our study of blood from febrile returned travelers back to 🇨🇦 @UofTIMS PhD student phenom @ruwandik demonstrated that 18% of specimens contained malaria, 15% had detectable EBV, 2% had dengue & 1% had hepatitis A virus (vaccine preventable):
wwwnc.cdc.gov/eid/article/22…

13/23 Our CATMAT guidelines recommend that febrile returned travelers undergo this basic set of primary laboratory investigations in order to exclude life-threatening, treatable, and communicable infectious diseases in this population. canada.ca/content/dam/ph…

14/23 Despite comprehensive & often exhaustive microbiological work-up, a diagnostic gap remains in febrile returned travelers. "Gap" of 22% observed in @GeoSentinel analysis, 7% in @AnnalsofIM W Africa analysis & 14% in our “Rapid Assessment of Febrile Travelers" seen locally.

15/23 Due to diagnostic gap & poor performing diagnostics for some infections (eg, typhoid), our CATMAT guidelines recommend empiric antimicrobial Rx for typhoid & rickettsial infections/lepto if 4 criteria below are fulfilled. FQs or Azi for typhoid, Doxy for rickettsial/lepto.

16/23 Some additional "rules" to remember about febrile returned travelers: 1st, Occam's razor does not apply to this population. Consider coinfections, esp. if signs sx & epi support >1. Eg, see our case published in @TMAID1:
ncbi.nlm.nih.gov/pubmed/31051263

& @ASTMH #TropMed19 posters

17/23 Another "rule" about febrile returned travelers is that they can have locally acquired infections that mimic those from tropics. Eg, influenza: circulates year-round in tropics & in season opposite to ours in S hemisphere. See our #JTravMed paper: academic.oup.com/jtm/article/19…

18/23 Here's another example of a locally-acquired infection from N America masquerading as malaria in a febrile traveler from India. Message: when labs don't make sense, go back to patient for more history! 90%+ medicine is patient's history.
ncbi.nlm.nih.gov/pmc/articles/P…

#Babesia

19/23 For more on our Rapid Assessment of Febrile Travelers (RAFT) program, which is a clinical adaptation of the @PHAC_GC CATMAT guidelines for use by EDs, see first analysis:
bmjopen.bmj.com/content/6/7/e0…

as well as our "app": bit.ly/RaFt

@StefanieKlowak @Bolsky

20/23 For a case-based discussion of considerations in febrile returned travelers w/ potential risk of viral hemorrhagic fever, see our @CMAJ
paper: ncbi.nlm.nih.gov/pmc/articles/P… & recent guidance from @PHAC_GC & @CDCtravel on EVD: canada.ca/en/public-heal… & wwwnc.cdc.gov/travel/disease…

21/23 For latest guidance on 2019-nCoV & travel see the following expert resources:

@CDCtravel: wwwnc.cdc.gov/travel/notices…

@WHO: who.int/emergencies/di…

Gov't Canada: travel.gc.ca/travelling/hea…

@PHAC_GC: canada.ca/en/public-heal…

@McGillTropMed @NaTHNaC @Paromita2015 @tropdocamcc

22/23 As with all work arising from my program, I am honored & privileged to mentor a wonderful team of trainees & staff who have contributed to many of the works cited above. Thank you to all who have helped me advance our understanding of fever in returning travelers! 🙌👏🙏🔥

23/23 Tagging those working with me in the Febrile Returned Travelers program: @AishaKhatib @MichaelKlowak @ruwandik @rachellau25 @HagopianEmma @shareeseclarke @StefanieKlowak @Bolsky @fjazuli @EricShao15 @melissaphuong @katfaithtan @DavidJamesHarri @AyoAyogirl @celinelecce_ 🙏🙏

And more from fever/malaria program: @rochellegmelvin @jason_kwan4 @michelledaodong @dylan_kain @AvinashMukkala @LeilaFMakhani @ShvetaBhasker 🙏🙏🔥🔥🔥🙌👏