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Abstract

  1. Top of page
  2. Abstract
  3. Methods
  4. Results
  5. Discussion
  6. Acknowledgments
  7. Declaration of Interests
  8. References

Background

Travelers to countries where rabies is endemic may be at risk of rabies exposure. We assessed rabies immunization of travelers attending a travel clinic in Thailand.

Methods

The medical charts of international travelers who came for preexposure (PrEP) or postexposure (PEP) rabies prophylaxis at 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 rabies exposures and 594 persons who came requesting PrEP, were studied. Of the travelers who received PEP, only 27 (14.3%) had been previously immunized against rabies and 141 (75.0%) cases experienced high-risk WHO category III exposure. Most of the incidents were unprovoked. Although promptly seeking medical services after the injuries, 114 (60.7%) travelers did not undertake any first-aid care for their wounds. Of these travelers, 19 (10.3%) received intradermal rabies vaccination as they could complete the series here. Rabies immunoglobulin was given to 118 of 121 (97.5%) patients. About one fourth of recipients could accomplish the full schedule at QSMI. Among visitors who requested PrEP, 454 (76.4%) persons had just started their first dose. Among all visitors, 263 (44.3%) were Japanese. The number of Japanese asking for PrEP was higher in 2006, the year when cases of imported human rabies to Japan were reported. This trend has sustained since then. Two (0.3%) travelers were bitten by suspected rabid dogs 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 are prone to the risks of rabies exposures. Of the 23,509 returning travelers seen at GeoSentinel clinics from six continents, 1.4% presented with animal-related injuries.[1] Most of the incidents happened in Asia and Africa. Forty-two rabies cases had been imported to the United States, Europe, and Japan during the last two decades.[2] Thailand, a well-established tourist destination with arrivals of over 10 million annually,[3] was mentioned as a common site of mammal bites (Table 1).[4-9] Through the improved accessibility of postexposure prophylaxis (PEP), some canine vaccination and intensive public education, the country has succeeded in decreasing annual human rabies fatalities from hundreds in the 1960s to <25 since the 2010s.[10] Nevertheless, the burden of canine rabies is still significant. Dogs are the rabies reservoir and principal source of exposures. Approximately 10 million domestic and free-roaming dogs have low rabies vaccination coverage.[11] Almost one third of submitted specimens for fluorescent antibody detection were confirmed as rabies infected.[12, 13] It is estimated that one million of the total Thai population of 65 million are bitten by dogs each year. Less than half of them receive PEP.[12] Dog bites occupied 5.3% of injuries seen in the emergency room at a university hospital in Bangkok.[14] The incidence of travelers being bitten or licked during an average stay of 1 month was 0.69 to 2.3 per 100 travelers, or 3.1 to 15.7 per 100 travelers, respectively.[15-17] Among these, 37.1 to 66.7% of exposed patients sought medical care. Only 11.6% to 18.1% of all travelers had complete preexposure rabies prophylaxis (PrEP) before their trip.[16, 17] This study was conducted to assess rabies immunization of foreign travelers attending a travel clinic in an epizootic area in Thailand.

Table 1. Mammal-associated injuries and rabies postexposure management of travelers[4-9]
Place of travel clinicsFrance, Australia, New ZealandNew ZealandUnited KingdomIsraelSwitzerlandNepal
  1. Data are number of travelers, unless otherwise indicated.

  2. Percentages; as compared with the total travelers in each study.

  3. ND = not documented; SEA = Southeast Asia; PrEP = preexposure prophylaxis; PEP = postexposure prophylaxis; RIG = rabies immunoglobulin.

Number of travelers26154139139056
Male : femaleND1.1 : 11.04 : 11.6 : 10.85 : 11 : 1.5
Mean age (year) (range)ND30.435 (2–84)2636 (median) (2–74)ND
Age < 15 yearsND9 (16.7%)Age <10 years (7; 5.0%)NDND2 (3.6%)
Main regions of injurySEA and North AfricaSouth Asia and SEAAsiaAsiaAsiaAsia
Common countriesThailand (52; 19.9%)Thailand (19; 35.2%)Thailand (31; 22.3%)

Turkey (31; 22.3%)

NDNDNepal (56; 100%)
Responsible dog139 (53.3%)36 (66.7%)69 (49.6%)6 (46.2%)50 (55.0%)32 (57.1%)
Sites of woundsSevere facial and hand injuries (20; 7.7%)Thigh and lower limbs (26; 48.1%)Lower limbs (67; 48.2%)Upper limbs (8; 61.5%)NDHead or face (1; 1.8%)
WHO CAT III197 (75.4%)46 (85.2%)ND7 (53.8%)NDND
Previous PrEP16 (6.1%)3 (5.6%)14 (10.1%)1 (7.7%)9 (10.0%)12 (21.4%)
Initiation PEP abroad133 (50.9%)54 (100%)86 (61.9%)4 (30.8%)54 (60.0%)
Indicated for RIG170 (65.1%)ND78 (56.1%)ND81 (90.0%)ND
Received RIG abroad19 (7.3%)7 (12.9%)3 (3.8%)ND7 (7.8%)
Received RIG in home country22 (8.4%)3 (5.6%)11 (7.9%)ND28 (31.1%)ND

Methods

  1. Top of page
  2. Abstract
  3. Methods
  4. Results
  5. Discussion
  6. Acknowledgments
  7. Declaration of Interests
  8. References

The Queen Saovabha Memorial Institute (QSMI) of the Thai Red Cross Society provides travelers with PrEP as well as PEP for prophylaxis or treatment of animal bites. The study was carried out retrospectively by reviewing the medical charts of all international travelers who received PrEP or PEP at the outpatient clinic of QSMI for 11 years from 2001 to 2011. Collected information included age, gender, nationality, history of antimalarial or immunosuppressive drugs used, date of exposure, interval before seeking medical attention, site of the wounds, grading of the severity of the exposures (WHO categories I to III), immediate first aid rendered, description of the responsible animals, place of accident, antirabies vaccination, and use of rabies immunoglobulin (RIG). All data were extracted from patient records, then anonymously entered and analyzed using the statistical software package spss version 21.0 for Windows (SPSS Inc., New York, NY, USA). The study was approved by the institute's ethics committee.

Results

  1. Top of page
  2. Abstract
  3. Methods
  4. Results
  5. Discussion
  6. Acknowledgments
  7. Declaration of Interests
  8. References

A total of 786 travelers were identified. Four individuals were excluded because of incomplete records. Of the remaining 782 travelers, 188 (median age 30 years, M : F = 2.1 : 1) came with animal-associated injuries and possible rabies exposures and 594 (median age 28 years, M : F = 1.8 : 1) came to receive PrEP (Figure 1). During 2001 to 2011, there were 32,256 PEP recipients and 6,276 PrEP recipients. International travelers accounted for 0.6% and 9.5% of all PEP and PrEP recipients, respectively.

image

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

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Among travelers who received PEP, most came from low endemicity countries in Europe and the Americas (Table 2). Only 27 (14.3%) patients were already immunized against rabies, while 157 (83.5%) cases had never received rabies vaccination. Of these patients, 141 (75.0%) experienced WHO category III exposures (wounds penetrating skin and bleeding). Although many patients promptly sought medical services, 114 (60.7%) patients did not perform any first-aid wound care (Table 3). There was no significant difference in prehospital management of wound care between travelers who had ever received rabies immunization and those who had never done so. There were mammal-associated injuries acquired in Bangkok, elsewhere in Thailand (especially in provinces with tourist attractions), and in other Asian countries. Most of the bites were unprovoked, occurring on roads or tourist spots from stray dogs, monkeys, or cats. Only three (2.4%) of the offending dogs were owned and annually vaccinated. Two dogs were proved to be rabid by direct fluorescent antibody test (dFAT). The vast majority of responsible dogs were not captured and examined. A few traveling patients had to attend at least two to three different hospitals during the PEP course and to do so in two to three different countries. Overall, 86 (45.7%) subjects had prior treatments from other hospitals in Thailand or abroad. The majority of patients received the conventional five-dose Essen intramuscular regimen. The rest received varied protocols such as the 2-1-1 (Zagreb) schedule (WHO approved) or the original or modified Thai Red Cross intradermal (TRC-ID) method. Suckling mouse brain vaccine was used in one traveler in Vietnam in 2007. Three (1.6%) patients, who attended different hospitals during their courses, received more than one schedule of rabies vaccination. They were initially given the Essen intramuscular regimen for PEP and later switched to TRC-intradermal protocol at other hospitals. Before attending QSMI, 34 travelers with WHO category III exposure did not receive RIG according to WHO recommendation as a result of unavailability or misinterpretation of the severity of exposure by local health care providers. Eventually, RIG was given to 118 of 121 (97.5%) patients where it was indicated. Two travelers appeared later than 7 days after having started vaccination elsewhere and RIG was contraindicated at this late time when native antibodies were appearing. One traveler refused RIG without giving any reason. Fifty (42.4%) patients received purified equine rabies immunoglobulin (ERIG). None of these developed serum sickness or other significant complications. About one fourth of recipients could finish their PEP schedules at QSMI. At least 28 (14.9%) patients had to continue the vaccination course abroad—either at their home countries or next destinations.

Table 2. Demographic data and characteristics of mammal-associated injuries with possible rabies exposures of 188 travelersa
 n (%)
  1. a

    Exclusive of local citizens of which there were an additional 32,256 PEP recipients.

  2. b

    Cambodia, Laos, Myanmar, Vietnam, the Philippines, Indonesia, Malaysia, India, Sri Lanka, Nepal, and China.

  3. c

    Bats, horse, otter, tiger, and gibbon.

Sex 
Male127 (67.6)
Female61 (32.4)
Age (year) (median 30 years; range 4–64 years) 
≤1510 (5.3)
16–3086 (45.7)
31–4559 (31.4)
46–6024 (12.8)
>609 (4.8)
Nationality (n = 183) 
European90 (49.2)
North American43 (23.5)
Asian38 (20.8)
Oceania (Australian, New Zealander)9 (4.9)
South American3 (1.6)
History of previous rabies immunization 
Preexposure prophylaxis20 (10.6)
Postexposure prophylaxis7 (3.7)
Incomplete pre- or postexposure prophylaxis4 (2.1)
Never157 (83.5)
Place of mammalian bite injury 
Bangkok50 (26.6)
Other provinces in Thailand90 (47.9)
Other countriesb48 (25.5)
Responsible mammals 
Dogs126 (67.0)
Ownerless94 (74.6)
Unknown status5 (4.0)
Owned, annually vaccinated3 (2.4)
Owned, not vaccinated8 (6.3)
Owned, unknown history of vaccination16 (12.7)
Monkeys28 (14.9)
Cats22 (11.7)
Other mammalsc12 (6.4)
Bite—wound location 
Extremities172 (91.5)
Face and head9 (4.8)
Trunk7 (3.7)
Rabies exposure according to WHO category 
Category I (touching or feeding of animals, licks on intact skin)3 (1.6)
Category II (nibbling of uncovered skin, minor scratches, or abrasions without bleeding)44 (23.4)
Category III (single or multiple transdermal bites or scratches, licks on broken skin, contamination of mucous membrane with saliva, exposure to bats)141 (75.0)
Table 3. Postexposure rabies prophylaxis (PEP) of 188 travelers
 n (%)
  1. QSMI = Queen Saovabha Memorial Institute.

  2. a

    Three cases did not receive PEP according to WHO category I exposure.

  3. b

    Patients who never received rabies immunization before.

First aid (wound care) after bite 
None114 (60.7)
Wash with only water19 (10.1)
Wash with water and soap32 (17.0)
Wash with water, soap, and antiseptic agent23 (12.2)
Time to receive postexposure prophylaxis after rabies exposure 
Within 24 hours116 (61.7)
Within 3 days138 (73.4)
Within 7 days164 (87.3)
Regimen (n = 185)a 
Postexposure prophylaxis 
Standard five-dose intramuscular regimen133 (71.9)
Thai Red Cross—intradermal regimen19 (10.3)
Zagreb regimen3 (1.6)
Booster immunization27 (14.6)
Others (more than one regimen)3 (1.6)
Rabies immunoglobulin administration for WHO category III exposure (n = 118)b 
QSMI 
Human rabies immunoglobulin54 (45.8)
Purified equine rabies immunoglobulin50 (42.4)
Other hospitals14 (11.8)
Postexposure prophylaxis course 
Complete course at QSMI54 (28.7)
Continue vaccination elsewhere in Thailand106 (56.4)
Continue vaccination abroad28 (14.9)

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 PrEP at 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 top five nationalities that received PrEP. The number of Japanese asking for PrEP was higher in 2006, the year with 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 their PrEP series was completed and full PEP schedule plus RIG were provided instead as <7 days since vaccination had elapsed. Forty-one (6.9%) travelers concurrently took antimalarial drugs such as mefloquine or doxycycline, and all received intramuscular rabies vaccination.

Table 4. Demographic data and preexposure rabies vaccination (n = 594)
 n (%)
  1. PrEP = preexposure prophylaxis; QSMI = Queen Saovabha Memorial Institute.

Sex 
Male383 (64.5)
Female211 (35.5)
Age (year) (median 28 years; range 3–72 years) 
≤1510 (1.7)
16–30364 (61.3)
31–45159 (26.7)
46–6051 (8.6)
>6010 (1.7)
Nationality (n = 585) 
Asian296 (50.6)
European179 (30.6)
North American87 (14.9)
Oceania (Australian, New Zealander)22 (3.7)
South American1 (0.2)
Preexposure rabies prophylaxis course 
Started first dose454 (76.4)
Required to complete schedule140 (23.6)
Complete three-dose of PrEP at QSMI 
Yes165 (27.8)
No429 (72.2)

Discussion

  1. Top of page
  2. Abstract
  3. Methods
  4. Results
  5. Discussion
  6. Acknowledgments
  7. Declaration of Interests
  8. References

As long as the rabies reservoirs in endemic regions are not controlled, travel in the affected area carries the risk of exposure. Owned and vaccinated domestic dogs in endemic zones cannot be considered entirely free of rabies. A single dose of rabies vaccine given to dogs was unable to reliably maintain protective antibody levels past 6 months, and 3% to 9% of rabid dogs had a history of rabies vaccination.[18, 19] In 2008 to 2011, owned dogs were responsible for over three fourths of human rabies cases in Thailand (Apirom Puanghat, personal communication, January 2013). Besides dogs and cats, various mammalian species were, although rarely, laboratory diagnosed as rabid. This included cats, monkeys, cattle, horses, one pet rabbit (bitten by a rabid rat), squirrels, bats, pigs, and sheep.[11] Thus, tourists must be educated to avoid any unnecessary contact with any mammals.

In the context of travelers, many could not arrange to have the five visits over a month required for PEP at a single health care provider. Different hospitals may then switch to different rabies vaccination schedules. Currently, there are at least four postexposure schedules being used worldwide.[20] The World Health Organization initiated recent efforts to simplify, standardize, and rationalize the multiple, complex, confusing, and prolonged postexposure rabies immunization schedules. WHO-recommended postexposure treatment is not yet uniformly provided in some developing countries. The main barriers are the shortage or lack of distribution of rabies biologics, and lack of or inadequate education of health care personnel in managing rabies exposures. Not providing RIG where it is indicated is of utmost concern. Human RIG is expensive and usually not even stocked in many countries. However, highly purified ERIG is now increasingly available in almost all Asian countries. It is safe and effective, yet travelers reporting to animal bite clinics often refuse receiving it to their own detriment when the human product is not available or not affordable. Such travelers often report to a clinic after returning home, and with much delay, when administering it is then contraindicated.[8] Any transdermal wound is classified by WHO as category III (severe exposure). It is neither the site nor size which determines the severity of an exposure but rather the fact that it has penetrated the skin. Another still common error is that the human or equine immunoglobulin is administered intramuscularly and not into the bite sites, the only sites where it has been shown to be effective and potentially life saving.[21]

Preexposure rabies vaccination for persons at increased risk by virtue of life styles and occupations has been recommended by WHO. Predicting the actual risks of exposure for a traveler is difficult. It depends on prevalence of canine and wildlife rabies, the traveler's activities, time spent in the high-risk region, and other unknown factors. Consideration also needs to be given to the availability of WHO level postexposure prophylaxis in that particular country. The threshold for recommending preexposure vaccination must be lowered if travel is to a region where WHO-approved rabies vaccines and immunoglobulins are not available. There are such locations which, nevertheless, attract many international tourists. When the exposed has previously received PrEP, only two booster injections within 3-day intervals would be needed and without RIG. Otherwise, a single-visit four-site intradermal booster regimen, consisting of four intradermal injections of 0.1 mL of rabies vaccine over both deltoids and thighs are an effective and convenient 1-day alternative.[20, 22] Even with a history of PrEP, the importance of immediate wound care and booster vaccination must be stressed. Following a PrEP schedule requires planning and time. Abbreviated PrEP schemes are now undergoing study.[23]

Our report has limitations inherent of a retrospective study at one center in one country with high awareness of the rabies threat. However, it represented the overview of a practice in realistic conditions of a travel clinic in canine-rabies region.

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

Acknowledgments

  1. Top of page
  2. Abstract
  3. Methods
  4. Results
  5. Discussion
  6. Acknowledgments
  7. Declaration of Interests
  8. References

We are grateful to Miss Nartanong Khumniphat for her secretarial support and Dr Lowell Skar for reviewing the manuscript.

Declaration of Interests

  1. Top of page
  2. Abstract
  3. Methods
  4. Results
  5. Discussion
  6. Acknowledgments
  7. Declaration of Interests
  8. References

The authors declare no conflict of interest in this study.

References

  1. Top of page
  2. Abstract
  3. Methods
  4. Results
  5. Discussion
  6. Acknowledgments
  7. Declaration of Interests
  8. References
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