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ORIGINAL ARTICLE

Rabies Immunization of Travelers in a Canine Rabies Endemic Area

Suda Sibunruang, MD,∗ Saowaluck Tepsumethanon, RN,∗ Natthasri Raksakhet, PN,∗ andTerapong Tantawichien, MD∗†

∗Queen Saovabha Memorial Institute (WHO Collaborating Centre for Research on Rabies Pathogenesis and Prevention), TheThai Red Cross Society, Bangkok, Thailand; †Division of Infectious Diseases, Department of Medicine, Faculty of Medicine,Chulalongkorn University, Bangkok, Thailand

DOI: 10.1111/jtm.12023

See the Editorial by Henry Wilde, pp. 139–142 of this issue.

Background. Travelers to countries where rabies is endemic may be at risk of rabies exposure. We assessed rabies immunizationof travelers attending a travel clinic in Thailand.Methods. The medical charts of international travelers who came for preexposure (PrEP) or postexposure (PEP) rabies prophylaxisat the Queen Saovabha Memorial Institute (QSMI), Bangkok, Thailand between 2001 and 2011 were retrospectively reviewed.Results. A total of 782 travelers, including 188 patients who presented with mammal-associated injuries and possible rabiesexposures and 594 persons who came requesting PrEP, were studied. Of the travelers who received PEP, only 27 (14.3%) hadbeen previously immunized against rabies and 141 (75.0%) cases experienced high-risk WHO category III exposure. Most of theincidents were unprovoked. Although promptly seeking medical services after the injuries, 114 (60.7%) travelers did not undertakeany first-aid care for their wounds. Of these travelers, 19 (10.3%) received intradermal rabies vaccination as they could completethe series here. Rabies immunoglobulin was given to 118 of 121 (97.5%) patients. About one fourth of recipients could accomplishthe full schedule at QSMI. Among visitors who requested PrEP, 454 (76.4%) persons had just started their first dose. Among allvisitors, 263 (44.3%) were Japanese. The number of Japanese asking for PrEP was higher in 2006, the year when cases of importedhuman rabies to Japan were reported. This trend has sustained since then. Two (0.3%) travelers were bitten by suspected rabiddogs before they completed their PrEP program.Conclusion. Rabies prophylaxis is an important decision for each traveler. It should be made before visiting endemic areas.

Travelers to countries where rabies is endemic areprone to the risks of rabies exposures. Of the

23,509 returning travelers seen at GeoSentinel clinicsfrom six continents, 1.4% presented with animal-related injuries.1 Most of the incidents happenedin Asia and Africa. Forty-two rabies cases hadbeen imported to the United States, Europe, andJapan during the last two decades.2 Thailand, awell-established tourist destination with arrivals of over

This study was partly presented as a poster at the 8th Asia-Pacific Travel Health Conference, Nara, Japan, October20–23, 2010.

Corresponding Author: Suda Sibunruang, MD, QueenSaovabha Memorial Institute, The Thai Red Cross Society,1871 Rama IV Road, Pathumwan, Bangkok 10330, Thailand.E-mail: sudapunrin@gmail.com

10 million annually,3 was mentioned as a commonsite of mammal bites (Table 1).4–9 Through theimproved accessibility of postexposure prophylaxis(PEP), some canine vaccination and intensive publiceducation, the country has succeeded in decreasingannual human rabies fatalities from hundreds in the1960s to <25 since the 2010s.10 Nevertheless, theburden of canine rabies is still significant. Dogs arethe rabies reservoir and principal source of exposures.Approximately 10 million domestic and free-roamingdogs have low rabies vaccination coverage.11 Almost onethird of submitted specimens for fluorescent antibodydetection were confirmed as rabies infected.12,13 It isestimated that one million of the total Thai populationof 65 million are bitten by dogs each year. Less thanhalf of them receive PEP.12 Dog bites occupied 5.3%of injuries seen in the emergency room at a universityhospital in Bangkok.14 The incidence of travelers beingbitten or licked during an average stay of 1 monthwas 0.69 to 2.3 per 100 travelers, or 3.1 to 15.7 per 100

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160 Sibunruang et al.

Table 1 Mammal-associated injuries and rabies postexposure management of travelers4–9

Place of travelclinics

France,Australia, New

Zealand New ZealandUnited

Kingdom Israel Switzerland Nepal

Number of travelers 261 54 139 13 90 56Male : female ND 1.1 : 1 1.04 : 1 1.6 : 1 0.85 : 1 1 : 1.5Mean age (year)

(range)ND 30.4 35

(2–84)26 36 (median)

(2–74)ND

Age < 15 years ND 9 (16.7%) Age <10 years(7; 5.0%)

ND ND 2 (3.6%)

Main regions of injury SEA and NorthAfrica

South Asia and SEA Asia Asia Asia Asia

Common countries Thailand(52; 19.9%)

Thailand(19; 35.2%)

Thailand(31; 22.3%)

Turkey(31; 22.3%)

ND ND Nepal(56; 100%)

Responsible dog 139 (53.3%) 36 (66.7%) 69 (49.6%) 6 (46.2%) 50 (55.0%) 32 (57.1%)Sites of wounds Severe facial and

hand injuries(20; 7.7%)

Thigh and lower limbs(26; 48.1%)

Lower limbs(67; 48.2%)

Upper limbs(8; 61.5%)

ND Head or face(1; 1.8%)

WHO CAT III 197 (75.4%) 46 (85.2%) ND 7 (53.8%) ND NDPrevious PrEP 16 (6.1%) 3 (5.6%) 14 (10.1%) 1 (7.7%) 9 (10.0%) 12 (21.4%)Initiation PEP abroad 133 (50.9%) 54 (100%) 86 (61.9%) 4 (30.8%) 54 (60.0%) —Indicated for RIG 170 (65.1%) ND 78 (56.1%) ND 81 (90.0%) NDReceived RIG abroad 19 (7.3%) 7 (12.9%) 3 (3.8%) ND 7 (7.8%) —Received RIG in

home country22 (8.4%) 3 (5.6%) 11 (7.9%) ND 28 (31.1%) ND

Data are number of travelers, unless otherwise indicated.Percentages; as compared with the total travelers in each study.ND = not documented; SEA = Southeast Asia; PrEP = preexposure prophylaxis; PEP = postexposure prophylaxis; RIG = rabies immunoglobulin.

travelers, respectively.15–17 Among these, 37.1 to 66.7%of exposed patients sought medical care. Only 11.6% to18.1% of all travelers had complete preexposure rabiesprophylaxis (PrEP) before their trip.16,17 This studywas conducted to assess rabies immunization of foreigntravelers attending a travel clinic in an epizootic area inThailand.

Methods

The Queen Saovabha Memorial Institute (QSMI) ofthe Thai Red Cross Society provides travelers withPrEP as well as PEP for prophylaxis or treatment ofanimal bites. The study was carried out retrospectivelyby reviewing the medical charts of all international trav-elers who received PrEP or PEP at the outpatient clinicof QSMI for 11 years from 2001 to 2011. Collectedinformation included age, gender, nationality, historyof antimalarial or immunosuppressive drugs used, dateof exposure, interval before seeking medical attention,site of the wounds, grading of the severity of the expo-sures (WHO categories I to III), immediate first aidrendered, description of the responsible animals, placeof accident, antirabies vaccination, and use of rabiesimmunoglobulin (RIG). All data were extracted frompatient records, then anonymously entered and analyzedusing the statistical software package spss version 21.0for Windows (SPSS Inc., New York, NY, USA). Thestudy was approved by the institute’s ethics committee.

Results

A total of 786 travelers were identified. Four individualswere excluded because of incomplete records. Of theremaining 782 travelers, 188 (median age 30 years,M : F = 2.1 : 1) came with animal-associated injuries andpossible rabies exposures and 594 (median age 28 years,M : F = 1.8 : 1) came to receive PrEP (Figure 1). During2001 to 2011, there were 32,256 PEP recipients and6,276 PrEP recipients. International travelers accountedfor 0.6% and 9.5% of all PEP and PrEP recipients,respectively.

Among travelers who received PEP, most camefrom low endemicity countries in Europe and theAmericas (Table 2). Only 27 (14.3%) patients werealready immunized against rabies, while 157 (83.5%)cases had never received rabies vaccination. Of thesepatients, 141 (75.0%) experienced WHO category IIIexposures (wounds penetrating skin and bleeding).Although many patients promptly sought medicalservices, 114 (60.7%) patients did not perform anyfirst-aid wound care (Table 3). There was no significantdifference in prehospital management of wound carebetween travelers who had ever received rabiesimmunization and those who had never done so. Therewere mammal-associated injuries acquired in Bangkok,elsewhere in Thailand (especially in provinces withtourist attractions), and in other Asian countries. Mostof the bites were unprovoked, occurring on roads or

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Rabies Immunization of Travelers 161

Figure 1 Number of travelers who received postexposure prophylaxis (PEP) and preexposure prophylaxis (PrEP) at QueenSaovabha Memorial Institute during 2001 to 2011.

tourist spots from stray dogs, monkeys, or cats. Onlythree (2.4%) of the offending dogs were owned andannually vaccinated. Two dogs were proved to be rabidby direct fluorescent antibody test (dFAT). The vastmajority of responsible dogs were not captured andexamined. A few traveling patients had to attend atleast two to three different hospitals during the PEPcourse and to do so in two to three different countries.Overall, 86 (45.7%) subjects had prior treatmentsfrom other hospitals in Thailand or abroad. Themajority of patients received the conventional five-doseEssen intramuscular regimen. The rest received variedprotocols such as the 2-1-1 (Zagreb) schedule (WHOapproved) or the original or modified Thai Red Crossintradermal (TRC-ID) method. Suckling mouse brainvaccine was used in one traveler in Vietnam in 2007.Three (1.6%) patients, who attended different hospitalsduring their courses, received more than one schedule ofrabies vaccination. They were initially given the Essenintramuscular regimen for PEP and later switched toTRC-intradermal protocol at other hospitals. Beforeattending QSMI, 34 travelers with WHO categoryIII exposure did not receive RIG according toWHO recommendation as a result of unavailabilityor misinterpretation of the severity of exposure by local

health care providers. Eventually, RIG was given to 118of 121 (97.5%) patients where it was indicated. Twotravelers appeared later than 7 days after having startedvaccination elsewhere and RIG was contraindicated atthis late time when native antibodies were appearing.One traveler refused RIG without giving any reason.Fifty (42.4%) patients received purified equine rabiesimmunoglobulin (ERIG). None of these developedserum sickness or other significant complications. Aboutone fourth of recipients could finish their PEP schedulesat QSMI. At least 28 (14.9%) patients had to continuethe vaccination course abroad—either at their homecountries or next destinations.

Among 594 individuals who received PrEP, 454(76.4%) persons just started their first dose and 165(27.8%) travelers received all three injections of PrEPat QSMI (Table 4). The rest may have had their follow-up elsewhere. Travelers from Japan (263; 44.3%), UK(51; 8.5%), the United States (49; 8.2%), Germany(33; 5.6%), and France (23; 3.9%) were the topfive nationalities that received PrEP. The number ofJapanese asking for PrEP was higher in 2006, the yearwith reported cases of imported human rabies in Japan,and this trend has sustained since then. Two (0.3%)travelers were bitten by suspected rabid dogs before

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162 Sibunruang et al.

Table 2 Demographic data and characteristics ofmammal-associated injuries with possible rabies exposures of188 travelers∗

n (%)

SexMale 127 (67.6)

Female 61 (32.4)Age (year) (median 30 years; range 4–64 years)

≤15 10 (5.3)16–30 86 (45.7)31–45 59 (31.4)46–60 24 (12.8)>60 9 (4.8)

Nationality (n = 183)European 90 (49.2)North American 43 (23.5)Asian 38 (20.8)Oceania (Australian, New Zealander) 9 (4.9)South American 3 (1.6)

History of previous rabies immunizationPreexposure prophylaxis 20 (10.6)Postexposure prophylaxis 7 (3.7)Incomplete pre- or postexposure prophylaxis 4 (2.1)Never 157 (83.5)

Place of mammalian bite injuryBangkok 50 (26.6)Other provinces in Thailand 90 (47.9)Other countries† 48 (25.5)

Responsible mammalsDogs 126 (67.0)

Ownerless 94 (74.6)Unknown status 5 (4.0)Owned, annually vaccinated 3 (2.4)Owned, not vaccinated 8 (6.3)Owned, unknown history of vaccination 16 (12.7)

Monkeys 28 (14.9)Cats 22 (11.7)Other mammals‡ 12 (6.4)

Bite—wound locationExtremities 172 (91.5)Face and head 9 (4.8)Trunk 7 (3.7)

Rabies exposure according to WHO categoryCategory I (touching or feeding of animals, lickson intact skin)

3 (1.6)

Category II (nibbling of uncovered skin, minorscratches, or abrasions without bleeding)

44 (23.4)

Category III (single or multiple transdermal bitesor scratches, licks on broken skin, contaminationof mucous membrane with saliva, exposure to bats)

141 (75.0)

∗Exclusive of local citizens of which there were an additional 32,256 PEPrecipients.†Cambodia, Laos, Myanmar, Vietnam, the Philippines, Indonesia, Malaysia,India, Sri Lanka, Nepal, and China.‡Bats, horse, otter, tiger, and gibbon.

their PrEP series was completed and full PEP scheduleplus RIG were provided instead as <7 days sincevaccination had elapsed. Forty-one (6.9%) travelersconcurrently took antimalarial drugs such as mefloquineor doxycycline, and all received intramuscular rabiesvaccination.

Table 3 Postexposure rabies prophylaxis (PEP) of 188travelers

n (%)

First aid (wound care) after biteNone 114 (60.7)Wash with only water 19 (10.1)Wash with water and soap 32 (17.0)Wash with water, soap, and antiseptic agent 23 (12.2)

Time to receive postexposure prophylaxis afterrabies exposure

Within 24 hours 116 (61.7)Within 3 days 138 (73.4)Within 7 days 164 (87.3)

Regimen (n = 185)∗

Postexposure prophylaxisStandard five-dose intramuscular regimen 133 (71.9)Thai Red Cross—intradermal regimen 19 (10.3)Zagreb regimen 3 (1.6)

Booster immunization 27 (14.6)Others (more than one regimen) 3 (1.6)Rabies immunoglobulin administration for

WHO category III exposure (n = 118)†

QSMIHuman rabies immunoglobulin 54 (45.8)Purified equine rabies immunoglobulin 50 (42.4)

Other hospitals 14 (11.8)Postexposure prophylaxis course

Complete course at QSMI 54 (28.7)Continue vaccination elsewhere inThailand

106 (56.4)

Continue vaccination abroad 28 (14.9)

QSMI = Queen Saovabha Memorial Institute.∗Three cases did not receive PEP according to WHO category I exposure.†Patients who never received rabies immunization before.

Discussion

As long as the rabies reservoirs in endemic regionsare not controlled, travel in the affected area carriesthe risk of exposure. Owned and vaccinated domesticdogs in endemic zones cannot be considered entirelyfree of rabies. A single dose of rabies vaccine given todogs was unable to reliably maintain protective antibodylevels past 6 months, and 3% to 9% of rabid dogs hada history of rabies vaccination.18,19 In 2008 to 2011,owned dogs were responsible for over three fourthsof human rabies cases in Thailand (Apirom Puanghat,personal communication, January 2013). Besides dogsand cats, various mammalian species were, althoughrarely, laboratory diagnosed as rabid. This includedcats, monkeys, cattle, horses, one pet rabbit (bitten bya rabid rat), squirrels, bats, pigs, and sheep.11 Thus,tourists must be educated to avoid any unnecessarycontact with any mammals.

In the context of travelers, many could notarrange to have the five visits over a monthrequired for PEP at a single health care provider.Different hospitals may then switch to different rabiesvaccination schedules. Currently, there are at least fourpostexposure schedules being used worldwide.20 The

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Rabies Immunization of Travelers 163

Table 4 Demographic data and preexposure rabiesvaccination (n = 594)

n (%)

SexMale 383 (64.5)Female 211 (35.5)

Age (year) (median 28 years; range 3–72 years)≤15 10 (1.7)16–30 364 (61.3)31–45 159 (26.7)46–60 51 (8.6)>60 10 (1.7)

Nationality (n = 585)Asian 296 (50.6)European 179 (30.6)North American 87 (14.9)Oceania (Australian, New Zealander) 22 (3.7)South American 1 (0.2)

Preexposure rabies prophylaxis courseStarted first dose 454 (76.4)Required to complete schedule 140 (23.6)

Complete three-dose of PrEP at QSMIYes 165 (27.8)No 429 (72.2)

PrEP = preexposure prophylaxis; QSMI = Queen Saovabha Memorial Institute.

World Health Organization initiated recent effortsto simplify, standardize, and rationalize the multiple,complex, confusing, and prolonged postexposurerabies immunization schedules. WHO-recommendedpostexposure treatment is not yet uniformly providedin some developing countries. The main barriers arethe shortage or lack of distribution of rabies biologics,and lack of or inadequate education of health carepersonnel in managing rabies exposures. Not providingRIG where it is indicated is of utmost concern. HumanRIG is expensive and usually not even stocked inmany countries. However, highly purified ERIG is nowincreasingly available in almost all Asian countries. It issafe and effective, yet travelers reporting to animalbite clinics often refuse receiving it to their owndetriment when the human product is not availableor not affordable. Such travelers often report to aclinic after returning home, and with much delay,when administering it is then contraindicated.8 Anytransdermal wound is classified by WHO as categoryIII (severe exposure). It is neither the site nor size whichdetermines the severity of an exposure but rather the factthat it has penetrated the skin. Another still commonerror is that the human or equine immunoglobulin isadministered intramuscularly and not into the bite sites,the only sites where it has been shown to be effectiveand potentially life saving.21

Preexposure rabies vaccination for persons atincreased risk by virtue of life styles and occupationshas been recommended by WHO. Predicting theactual risks of exposure for a traveler is difficult. Itdepends on prevalence of canine and wildlife rabies,

the traveler’s activities, time spent in the high-riskregion, and other unknown factors. Consideration alsoneeds to be given to the availability of WHO levelpostexposure prophylaxis in that particular country. Thethreshold for recommending preexposure vaccinationmust be lowered if travel is to a region whereWHO-approved rabies vaccines and immunoglobulinsare not available. There are such locations which,nevertheless, attract many international tourists. Whenthe exposed has previously received PrEP, only twobooster injections within 3-day intervals would beneeded and without RIG. Otherwise, a single-visit four-site intradermal booster regimen, consisting of fourintradermal injections of 0.1 mL of rabies vaccine overboth deltoids and thighs are an effective and convenient1-day alternative.20,22 Even with a history of PrEP,the importance of immediate wound care and boostervaccination must be stressed. Following a PrEP schedulerequires planning and time. Abbreviated PrEP schemesare now undergoing study.23

Our report has limitations inherent of a retrospectivestudy at one center in one country with high awarenessof the rabies threat. However, it represented theoverview of a practice in realistic conditions of a travelclinic in canine-rabies region.

In conclusion, this study has shown the size of therisk of rabies to travelers and what travel clinics arefacing in Southeast Asia. Education of travelers beforethey leave is the effective method to reduce the risk.

Acknowledgments

We are grateful to Miss Nartanong Khumniphat for hersecretarial support and Dr Lowell Skar for reviewingthe manuscript.

Declaration of Interests

The authors declare no conflict of interest in this study.

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Pura Bukit Sari temple at the center of Sangeh forest in Bali is called the ‘‘Holy Monkey temple’’. Over 1,000 monkeys live aroundand inside the temple which was built by the Mangwi royal family in the 17th century. Since 2008, there has been a number ofrabies outbreaks reported in Bali. In January 2012, local authorities lifted a health alert on the disease (Jakarta Globe, July 21,2012). Photo Credit: Nicolas Bossard (Setting: Pura Bukit Sari temple, Bali)

J Travel Med 2013; 20: 159–164