Rabies risk Dr. Philippe Gautret Institut Hospitalo Universitaire - PDF document

6/19/2019 Rabies risk ‐‐ Dr. Philippe Gautret Institut Hospitalo ‐ Universitaire Méditerranée Infection, Unité de Recherche en Maladies Infectieuses et Tropicales Emergentes URMITE CNRS ‐ IRD UMR6236 EuroTravNet Marseille, France RABIES IS A ZOONOSE… 1 2 Annual number of rabies death globally in 2015 : 59 000 (95% CI, 25,000– 159,000) deaths * *probability decision ‐ tree approach (community Human rabies geographical surveys, large ‐ scale verbal autopsy surveys, active surveillance and contact tracing) distribution > 99% resulting from dog bites > 40% in chidren < 15 years Hampson et al., PLOS Neglected Tropical Diseases, 2015 WHO, WER, 2017 3 4 5 6 1

6/19/2019 Number of rabies death globally in 2015 TOP COUNTRIES World : 59000 ASIA: INDIA (35%), CHINA, THE PHILIPPINES Asia: 59.6% AFRICA: NO RELIABLE DATA AMERICA: HAITI & BOLIVIA MIDDLE EAST: YEMEN & Africa: 36.4% IRAQ 4 % 7 8 Résurgence de la rage du renard en Italie (2008) De Benedictis et al., EuroSurv, 2008 Rabies Bulletin Europe, 2013 9 10 Résurgence de la rage du renard en Grèce (2012) Travel ‐ associated human rabies Tsiodras et al., EuroSurv, 2013 11 12 2

6/19/2019 60 cases in 1990 ‐ 2012 10 new cases in 2013 ‐ 2019 • Taiwan ex. Philippine (migrant) • US ex. Guatemala (Migrant) • The Netherlands ex. Haïti (not documented) • The Netherlands ex. India (Indian married a Dutch) • France ex. Mali (VFR) • UK ex. India (not documented) • France ex. Sri Lanka (Tourist) • UK ex. Morocco (Tourist) • Qatar ex. Nepal (Migrant) • Norway ex. Philippines (Tourist) 13 14 7 1 17 29 14 • 2.6 cases per year, increase from 2004 Rabies cases among international travelers 1990 ‐ 2015 15 16 Main points • Mean incubation time 274 • Adult travelers (83%) days (9 months) • Men (75%) • 9 case < 30 days • Residence in Europe (57%) • 1 case 12 days after dog bite and US (27%) in India • Tourists + business + • 1 case 15 days after bat bite expatriates (57%) ‐ VFR + in Mexico migrants (43%) • 1 case 5 years after • Dogs (85%) immigration from China • 1 case 8 years after dog exposure in Brazil • 1 case 10 years after dog bite in Myanmar 17 18 3

6/19/2019 Conclusions • Diagnosis chalenging with multiple missed diagnosis – Low index of suspicion – Negative history of animal bite – Atypical presentation (Guillain ‐ Barré, sore ‐ throat infection, orthopedic, acute psychiatric disorder…) – Long incubation time • 8% rabies PEP in country of exposure, 100% mortality 19 20 Meta ‐ analysis • 1970 ‐ 2008 (38 year period study) • 9 published surveys • > 1 270 000 tourists (denominator) • > 11 000 expatriates (denominator) • > 600 injured travelers • Exposure in Africa, Asia, Latin America and Animal ‐ related injuries requiring The Middle East rabies PEP among travelers 21 22 The Steffen tree monthly incidence per 100 travelers 1997 ‐ 2012 2697 injured travelers receiving rabies PEP (1.5%) 0.4% (our 45 sites estimate) 74% seen after travel 25% seen during travel Origin: Western Europe: 32%, North East Asia: 17%, Australia New Zealand: 17%,South East Asia: 14%, North America: 10% 23 24 4

6/19/2019 300 2.5% Dog NHP Cat Bat Other % of records "y=0.0015x+0.006" • 42% in South East Asia, 32% other Asian countries, 9% Africa, 7% Latin America, 3% 250 2.0% Middle East : top countries : Thailand, Number of GeoSentinel Patients Percent of GeoSentinel Patients 200 Indonesia, Nepal, China, India . 1.5% 150 • Median travel duration : 15 days (patients 1.0% seen after travel), 20 days before presenting 100 (patients seen during travel) 0.5% 50 • Animal species: 60% dog, 24%, NHP, 10% cat, 2% bat 0 0.0% 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 Year • 2/3 of NHP exposure occured in Asia, 90% occured in tourists 25 26 • Most injured individuals reported to GeoSentinel are relatively young tourist travelers originating Age, gender, reason for travel and from developed countries, corresponding to the duration of travel are not good overall traveler population seen at GeoSentinel indicators for risk ‐ based decisions. sites. Travelers injured by potentially rabid animals do not present specific demographic characteristics compared to other ill travelers and therefore targeting reinforcement of preventive measures cannot be based on demographic factors alone. 27 28 Geographic destination is the strongest determinant of rabies exposure in travelers and should be considered in preventive vaccination decisions. 29 30 5

6/19/2019 Post ‐ exposure prophylaxis 31 32 WHO Stategic Advisatory Group of Risk assessment Experts (SAGE) on immunization • Rabies vaccines: WHO Position paper – April 2018 (WER, 16, 2018, 93:201 ‐ 220) 33 34 35 36 6

6/19/2019 37 38 39 40 41 42 7

6/19/2019 Naive individual IM (1 ml) 1x 1x 1x 1x 1x ESSEN D 0 D 3 D 7 D 14 D 28 Not recommanded anymore by WHO 1x 1x 1x 1x 4 ‐ dose ESSEN D 0 D 3 D 7 D 14-28 ZAGREB 2x 1x 1x D 0 D 3 D 7 D 14 D 21 IPC 2x 2x 2x ID (0.1 ml) D 0 D 3 D 7 D 14 D 21 + RIG in category III exposure 43 44 Immunized individuals 1x 1x IM (1 ml) D 0 D 3 1x 1x ID (0.1 ml) D 0 D 3 4x ID (0.1 ml) D 0 RIG is not indicated 45 46 47 48 8

6/19/2019 Effective • Additional IM administration of any remaining RIG at a site distant to the wound is a common 100% practice. Its benefits are likely to be very limited. Not recommended anymore. • Data from rabies ‐ endemic setting have shown that even in the absence of RIG, with thorough wound washing plus immediate vaccination and completion of the PEP course > 99% patients survive. 49 50 A few points For dog, cat and ferret ‐ related injuries • PEP should be administered as soon as • If the animal remains healthy for 10 days possible starting from the date of the bite, PEP can be • There is no time limit to administer PEP in discontinued case of type III exposure (however, if vaccine In any case supply is limited, vaccine can be reserved for exposure that occured within 12 months) • When possible, suspect animals should be • There are no contra ‐ indications to PEP humanely euthanized and tested for rabies. PEP • In case of repeted exposure < 3 months after can be discontinued if the animal is proved by previous PEP, only wound treatment is appropriate laboratory examination to be free required of rabies 51 52 Potentially immunocompromized RIG patients • If CD4 < 200/mm3, use RIG in both category II and III exposure, even in previously • Compartment syndrome may limit the immunized patients. amount of RIG that can be used when • A 3 ‐ visit vaccination schedule should be infiltrating fingers. followed (ID or IM – D0, 7, 21 ‐ 28) or a 2 ‐ visit • Can be diluted with physiological buffered schedule (ID or IM, D0, 7) with serological saline for large and multiple wounds. testing 2 ‐ 4 weeks after first rabies vaccine administration to assess whether an additional vaccine administration is needed. 53 54 9

6/19/2019 Making things more complicated 55 56 Same protocole for category II and III exposure (ESSEN + RIG in naive patients and D0, 3 in immunized patients) 4 ‐ dose ESSEN instead of 5 doses 57 58 Naive individual Immunized individuals IM (1 ml) 1x 1x 4 ‐ dose ESSEN (US) IM (1 ml) D 0 D 3 1x 1x 1x 1x D 0 D 3 D 7 D14 RIG is not indicated + RIG in category II and III exposure 59 60 10

6/19/2019 Naive individual IM (1 ml) 1x 1x 1x 1x 1x ESSEN D 0 D 3 D 7 D 14 D 28 2x 1x 1x ZAGREB D 0 D 3 D 7 D 14 D 21 2x 2x 2x ID (0.1 ml) D 0 D 3 D 7 D 14 D 21 + RIG in category III exposure 61 62 Immunized individuals 1x 1x IM (1 ml) D 0 D 3 1x 1x ID (0.1 ml) D 0 D 3 4x ID (0.1 ml) D 0 RIG is not indicated 63 64 Naive individual Immunized individuals IM (1 ml) 1x 1x 4 ‐ dose ESSEN (UK) IM (1 ml) D 0 D 3-7 1x 1x 1x 1x D 0 D 3 D 7 D21 RIG is not indicated + RIG in category II and III exposure 65 66 11

6/19/2019 Thank you for your attention philippe.gautret@ap-hm.fr 67 12