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Abstract

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

Background. In 2009, 58.6 million UK residents traveled abroad. Of these, 49.5 million (84.5%) visits were to Europe and North America and 9.1 million (15.5%) were to other parts of the world. Rabies is widely distributed and continues to be a major public health issue in many developing countries. The UK is free of rabies in carnivore host species, although cases of rabies in bats have been reported. This study examined the rabies postexposure prophylaxis (PEP) service from 2000 to July 2009 at the Liverpool School of Tropical Medicine.

Methods. Medical records of patients who attended the clinic for rabies PEP were reviewed.

Results. During the study period, 139 patients were treated for possible rabies exposure. The mean age was 35 years. Thailand and Turkey each accounted for 31 (22.3%) cases. Sixty-nine (49.6%) of those seen were due to dog bites. Most injuries involved a lower limb (n = 67, 48.2%) or hands (n = 26, 18.7%). Eighty-six (61.9%) cases had initiated rabies PEP overseas, but only 3 of the 78 (3.8%) meeting UK criteria for rabies immunoglobulin (RIG) received it while overseas. Only an additional 11 patients received RIG on return to the UK; most were seen more than 7 days after initiation of PEP. The median time from exposure to receiving rabies PEP was 1 day (range: 0–1,720). Only 14 (10.1%) had received preexposure rabies vaccination.

Conclusions. The majority of travelers seeking PEP at this clinic initiated treatment overseas. Most had not received RIG abroad, when it would have been appropriate. Initiation of appropriate treatment is often delayed and is a concern to those without preexposure rabies immunization. In view of the scarcity of RIG, travelers need to be aware of the risks, consider preexposure immunization, and present early for PEP.

Rabies is a viral zoonosis caused by rabies virus of Lyssavirus genus and the family Rhabdoviridae. The term rabies in Latin means “madness.”1 It causes acute encephalitis and is typically transmitted from the saliva of a rabid animal via a bite, scratch, or mucous membrane exposure. Rabies is almost invariably fatal if postexposure prophylaxis (PEP) is not administered before the development of symptoms. Prevention relies on a combination of interventions including the control of rabies in the animal population, administration of preexposure immunization to individuals at risk, and administration of PEP to exposed individuals.

Most of the burden of rabies is in Asia and Africa: mortality from rabies is estimated at 55,000 per year and results in 1.74 million disability adjusted life years per year.2 In 2009, 58.6 million UK residents traveled abroad. Of these, 49.5 million (84.5%) visits were to Europe and to North America and 9.1 million (15.5%) to other parts of the world. Of these, 2.8 million (4.8%) were to Asia, predominantly to India, Pakistan, and Thailand.3

The UK has been free of rabies in carnivore host species since 1922. However, it is recognized that UK bats carry lyssaviruses (European bat lyssaviruses) types 1 and 2, with one bat handler dying of rabies in 2005.4–6 There have been 24 cases of human rabies in the UK since 1902, with 5 cases in the last 10 years.7–10 Four of these cases were imported and none had received PEP (Table 1).

Table 1.  Human rabies cases in UK (2000–2009)
YearGenderAgeCountryMammalInjury/risk factorsPurpose
  1. VFR = visiting friends and family.

2008F30sSouth AfricaDogScratchVolunteer
2005F37IndiaDogBiteTravel
2002M55UKBatBat handlerWork
2001F52NigeriaDogBiteUnknown
2001M55PhilippinesDogBiteVFR

In the UK, PEP with vaccine and immunoglobulin is administered by different health care providers, including general practitioners, accident and emergency departments, and specialized services. Liverpool School of Tropical Medicine (LSTM) is one of the major travel centers that administer PEP. The Health Protection Agency (HPA) provides guidance and a centralized supply of human rabies immunoglobulin (HRIG) and postexposure vaccine for PEP, based on individual risk assessment, which takes into account the nature of injury, the immune status of the traveler, and the risk of rabies in the country involved.11 Approximately 3,500 vials of vaccines and 1,200 doses of immunoglobulin are used per year for PEP in the country, with a 50% increase registered between 2006 and 2008 [3,062 vials of vaccine in 2006 to 4,622 vials in 2008 and 1,020 doses of rabies immunoglobulin (RIG) in 2006 to 1,476 doses in 2008] (H. Kirkbride, personal communication, September 2009). It is important that appropriate PEP is given to those who are at risk. This study examined the rabies PEP service at the LSTM in the last 10 years.

Methods

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

Medical records of all patients who presented to the LSTM for rabies PEP from January 2000 to July 2009 were reviewed. Data regarding age, gender, country of exposure, the animal implicated in the exposure, prior preexposure vaccination, postexposure management with immunoglobulin and/or vaccine, site of injury, and time delay between date of exposure and treatment initiation were collected. Some travelers had started the treatment overseas and we considered human diploid cell vaccine (HDCV), purified chick embryo cell vaccine (PCECV), or purified vero cell rabies vaccine (PVRV) to be appropriate, as indicated in the HPA guidelines. These vaccines can be safely interchanged.11 The management of the exposure was compared with HPA guidelines on the basis of the risk assessment (Table 2). Data analysis was performed using SPSS software (version 13 for Windows; SPSS Inc, New York, USA).

Table 2.  Risk assessment and postexposure management following an exposure. (Adapted from Clinical Rabies Service, HPA, April 2010)
Category of exposureImmune status of individualPEP
  1. PEP = postexposure prophylaxis.

  2. Category I = touching or stroking of animals.

  3. Category II = licks of the skin or other contact with saliva, minor scratches and bruising without bleeding, and minor bites without breaking of skin.

  4. Category III = single or multiple transdermal bites or scratches and licks on broken skin, major bites (multiple or single on face, head, finger, or neck), and contamination of mucous membrane with saliva.

  5. Fully immunized refers to at least three documented doses of intramuscular rabies vaccine or documented rabies antibody titers of at least 0.5 IU/mL.

INot immuneNo PEP
IINot immuneFive doses of vaccines
 Fully immunizedTwo doses of vaccines
IIINot immuneFive doses of vaccines + RIG
 Fully immunizedTwo doses of vaccines

Results

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

A total of 142 patients attended PEP (Figure 1). Three of the medical records were not available and these were omitted from the analysis. Of the remaining 139 patients, 68 (48.9%) were female and 71 (51.1%) were male. The mean age of the cases was 35 (range: 2–84, SD: 16.8) with 8 missing data. Seven (5.3%) were younger than 10 years and 4 (2.9%) were older than 65 years (Figure 2). Exposures predominantly occurred in Thailand (31; 22.3%) and Turkey (31; 22.3%). Other countries involved were India (10; 7.2%) and Sri Lanka (5; 3.6%) (Figure 3). Most injuries involved the lower limb (67; 48.2%) followed by the hands (26; 18.7%). Other sites of injuries include the trunk (25; 18%). Four patients (2.9%) had multiple sites of injuries. Dogs were implicated in the majority (69; 49.6%) of exposures, followed by cats (32; 23%) and monkeys (23; 16.5%). There were seven (5%) exposures to bats (Figure 4). Two individuals did not have any animal exposure, but one had involved a contact with a positive rabies case abroad, with vomitus spilled on the body, and the other was a worried wife whose husband had been bitten by a confirmed rabid dog at multiple sites of the body. Most documented exposures were described as unprovoked (65; 46%). However, 27 (19%) individuals had no documentation of whether exposures were provoked.

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Figure 1. Number of patients for postexposure rabies treatment per year in Liverpool School of Tropical Medicine (LSTM). Data up to July 2009.

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Figure 2. The age distribution of individuals who presented for rabies postexposure prophylaxis.

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Figure 3. Areas of exposure by percentage. Others: Two (1.4%) exposures in each of the following: Brazil, Philippines, Kenya, Morocco, Namibia, Peru, Romania, Russia, South Africa, Spain, Tunisia, and United States. One (0.7%) exposure in each of the following: Argentina, Australia, Belize, Bolivia, Denmark, Ecuador, France, Gambia, Greece, Guatemala, Haiti, Indonesia, Latvia, Malaysia, Nicaragua, Oman, Portugal, Tanzania, United Arab Emirates, Vietnam, and Zambia.

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Figure 4. Type of animal exposure. “Others” are bites by a rat, bite by a chipmunk, exposure to vomitus from a child with rabies, and wife with husband bitten at multiple sites by a dog.

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PEP had been initiated overseas in 86 (61.9%) of the cases. Only 3 of the 78 (3.8%) cases meeting the UK criteria for administration of RIG received it while overseas. An additional 11 patients with initial treatment overseas received RIG on return to the UK; most patients were seen more than 7 days after the initiation of PEP. Because an antibody response to the active immunization is presumed to have occurred after 7 days, administration of RIG is unnecessary.12 Only 10.1% of the exposed travelers had received preexposure immunization.

The median time from exposure to receiving rabies PEP was 1 day (range: 0–1,720 days; interquartile range: 0–7 days), regardless of whether it was initiated overseas or in the UK. The extreme delay in four individuals (151–1,720 days) is explained by the fact that their significant animal exposure and injury was only discovered during their pretravel consultation for another trip. Current advice is that rabies PEP is given for significant exposure, regardless of the time interval from the exposure.

One person received PEP following an exposure to bats in Australia. Although Australia is described as rabies free,11 Australian bat lyssaviruses are found in the country13,14 and there have been fatal cases of rabies after exposure to bats in Australia.15,16 National recommendations are that PEP is given after exposure to bats in Australia.13

Discussion

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

This study looked at 10 years of data from a major tropical and travel center in Northwest England, which provides rabies PEP service. The travel clinic has an average 9,000 visits per year. In line with UK guidelines, preexposure vaccination with rabies is currently only recommended for individuals with prolonged travel to a rabies endemic country; occupational risks such as animal handlers, veterinary staff or wildlife workers; children who are less likely to report an injury; and for travelers to places where medical assistance is less reliable.

In our study, individuals aged 20–50 (62.6%) were most at risk, with the extremes of age making up less than 10% of the cohort, contrasting with reports from New Zealand that suggested children remained a vulnerable group.17 This indicates a difference in the mean age group of the travelers who visited our center, compared to those who sought PEP in New Zealand. It is important to educate all ages about the risk of rabies, the importance of prompt reporting of all injuries, and the value of vaccination.

Southeast Asia is the region where most rabies exposures occurred. These places are considered to be of high risk for rabies2 and although only 4.8% of total visits by UK residents are to Asia, more than half of all rabies exposures occurred there. We noted that the number of exposures to Thailand is similar to that of Turkey. However, there are 1.6 million (2.8%) visits to Turkey and 0.3 million (0.6%) visits to Thailand. Hence, there is greater risk of exposure in Thailand than in Turkey. Although we did not record formal data on the duration of these trips, our experience suggests that most travelers whom we see going to these destinations are on short-term holidays. Moreover, medical care would have been readily available in these countries. Hence, most of these travelers would not fulfill the criteria for rabies vaccination before travel.

Dogs continued to be the predominant animal involved in the exposures. It is not known if the animals were proven to be rabid subsequently. Seven animals were known to be alive 15 days after the exposure incident and hence the rabies PEP was stopped. In general, we have noticed that individuals either leave before the completion of 15 days of observation or are unaware of the need to do this. The 15 days of observation is based on the HPA guidelines, differing from the World Health Organization (WHO) guidelines.11,18

The median time to PEP treatment was 1 day, regardless of whether treatment was initiated overseas or in the UK. Despite this, 25% had delays of more than 7 days, eight received PEP only after 100 days, and four were only being identified when receiving travel advice for a subsequent trip. Unfortunately, we do not have documentation about whether these individuals had received advice prior to their trip about the urgency of seeking treatment after an injury by a potentially rabid animal. We do not have any follow-up on those who had failed to receive RIG. However, no other clinical rabies cases in humans were reported in the UK other than those in Table 1. Despite rapid vaccination in the majority of our patients, few received RIG concurrently if PEP was commenced overseas, even though they met the UK criteria for RIG. The RIG is underutilized for various reasons. This not only reflects on the worldwide scarcity of the RIG but also on a lack of understanding of the potential severity of rabies, the availability of vaccination, and the need of RIG, if there has not been a preexposure vaccination.18,19

Overall, our data suggest that the traveler requires further education about the risk of rabies when they travel overseas: in addition to travel clinics, travel agencies, general practitioners, and nurses can all play a role in providing information to prospective travelers. Only 10.1% of the people treated in our clinic had received rabies immunization prior to travel. In view of the problems accessing RIG, travel medicine practitioners should inform all travelers about the risk of rabies, what initial first aid measures to perform in the event of an exposure, and to consider a course of rabies preexposure vaccination to simplify treatment, thereby removing the necessity of immunoglobulin if a potential rabies exposure occurs. GeoSentinel and WHO recommend that the rabies preexposure vaccination be given to all travelers going to rabies endemic countries where immediate medical care is limited, regardless of duration of travel because of the scarcity of immunoglobulin.18,20,21 However, such a change in policy for the UK would require careful assessment of the cost benefit of this approach for the traveler, in view of the rarity of exposure to this disease in this group.

Declaration of Interests

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

The authors state they have no conflicts of interest to declare.

References

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