Travel Medicine and Infectious Disease (2013) 11, 335e336
Available online at www.sciencedirect.com
ScienceDirect journal homepage: www.elsevierhealth.com/journals/tmid
EDITORIAL
Intradermal pre-exposure rabies vaccination. Promises and pitfalls KEYWORDS Intradermal rabies vaccine
In this special edition of Travel Medicine and Infectious Disease (TMAID), focusing on skin, it is timely to think about the intradermal (ID) rabies vaccine. Warrell published an excellent review of rabies vaccine in TMAID in 2012 [1]. The paper by Lau et al. [2] published in this issue of TMAID investigates the use of a different brand of rabies vaccine, using the modified intradermal regime published in 2011 with Human Diploid Cell Vaccine (HDCV) [3] The authors provide support for the efficacy of this regime when using Rabipur as opposed to HDCV. The use of ID rabies vaccine was described in 1976 [4], with the promise of allowing cheaper protection from a disease, which has been feared throughout history. Although deaths in travellers are rare (60 reported cases 1990e2012 [5]), rabies risk exposures are relatively common (2e13/1000 travellers per month, [6,7]). In travellers who are aware the horrors of this untreatable disease, a potential rabies exposure can be stressful, and cause major disruption to travel plans in the quest for appropriate treatment. The advice commonly given to travellers is “Your trip is short, so avoid petting dogs, and seek treatment if bitten” however this does not adequately deal with the issue of rabies prevention. “Trip is short” may initially sound plausible, but duration of trip is not a reliable defence against exposure. Rabies deaths have been observed in travellers after trips of two weeks or less [5]. The study [8] reported the mean time to injury was 15.3 days after departure from Australia and 88% were exposed within 30 days of arrival. “Avoid petting dogs” is potentially misleading to travellers. Geosentinel in 2007 reported [6] that dogs were responsible for only 51.3% of traveller’s exposures, and monkeys 21.2% (this was prior to the outbreak of rabies in
Bali.) Rabies exposures in travellers in two recent studies in Australia [8,9] reported 35.8% and 42% respectively were from dogs. Both studies noted more exposures from monkeys 49.4% and 45% respectively (especially in Bali). One could perhaps say “Avoid contact with mammals” however travellers may not have a choice. The mammals are sometimes the ones initiating contact. In study [8] in 40% of the exposed travellers, the mammal initiated the contact, and traveller initiated contact included activities like taking photos or shooing the animal. Most travellers would not perceive these as high risk animal interactions. In the NSW study published in this edition [9] the dog initiated contact in 38.0%. “Seek treatment if bitten” is a good plan in theory, but the difficulties of accessing proper post exposure treatment are twofold (finding a well trained provider with knowledge of current best practice, and finding the rabies immune globulin) and well described [10]. The paper by Kardamanidis et al. published in this edition concluded, “Opportunities for increasing pre-exposure treatment amongst individuals likely to be exposed should be promoted.” ID rabies vaccination provides this much needed opportunity for increasing pre-exposure treatment amongst individuals likely to be exposed. It also poses unique challenges to the practitioner: The recommendation of an off label vaccine, the storage of preservative-free, single dose rabies vaccine vials for multi-dose use, and the administration of the technically different intradermal technique, makes the ID option more suitable to larger travel clinics. Multidose ID regimes [2,3], have the advantage of decreasing the storage time required for single use vials used for ID courses. The occasional vaccinee who, for
1477-8939/$ - see front matter ª 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.tmaid.2013.10.007
336 no apparent reason, fails to generate an antibody level over the magic bar of 0.5 IU/ml, means that many travellers are subjected to blood tests in addition to their ID rabies course. To complicate matters, the level of 0.5 IU/ml is somewhat arbitrary and not a recognized correlate of protection. The criticism of rabies vaccine being especially expensive is fading. Costs of other vaccine are climbing to level of the rabies vaccine and more. The recommendation from the World Health Organisation that booster doses of rabies vaccines are not required [11] means pre-travel rabies vaccine is a long-term investment. ID vaccine is a useful solution to a niggling pre-travel problem. The tendency for travellers to present for their pretravel consultation closer and closer to their departure date adds a growing impetus for rapid pre-exposure rabies vaccination. Nirvana would perhaps involve one vial of IM rabies given ID in 4e8 sites, prior to sending the traveller on their merry way, safe in the knowledge of their adequate antibodies in 14 days. This has been used in some small studies [4] but as so often stated “further research is needed.”
Editorial
[4]
[5]
[6]
[7]
[8] [9]
[10]
Conflict of interest [11]
None declared.
References [1] Warrell MJ. Current rabies vaccines and prophylaxis schedules: preventing rabies before and after exposure. Travel Med Infect Dis 2012;10:1e15. [2] Lau Colleen L, Hohl Norman. Immunogenicity of a modified intradermal pre-exposure rabies vaccination schedule using a purified chick embryo cell vaccine. An observational study. Travel Med Infect Dis 2013;11:427e30. [3] Mills DJ, Lau CL, Fearnley EJ, Weinstein P. The immunogenicity of a modified intradermal pre-exposure rabies
vaccination ScheduledA case series of 420 travelers. J Travel Med 2011;18:327e32. Turner GS, Aoki FY, Nicholson KG, Tyrrell DA, Hill LE. Human diploid cell strain rabies vaccine. Rapid prophylactic immunisation of volunteers with small doses. Lancet 1976;1: 1379e81. Carrara P, Parola P, Brouqui P, Gautret P. Imported human rabies cases worldwide, 1990e2012. PLoS Negl Trop Dis 2013; 7:e2209. Gautret P, Schwartz E, Shaw M, Soula G, Gazin P, Delmont J, et al. Animal-associated injuries and related diseases among returned travellers: a review of the geoSentinel surveillance network. Vaccine 2007;25:2656e63. Piyaphanee W, Kittitrakul C, Lawpoolsri S, Gautret P, Kashino W, Tangkanakul W, et al. Risk of potentially rabid animal exposure among foreign travelers in southeast asia. PLoS Negl Trop Dis 2012;6:e1852. Mills DJ, Lau CL, Weinstein P. Animal bites and rabies exposure in Australian travellers. Med J Aust 2011;195. Kardamanidis K, Cashman P, Durrheim DN. Travel and nontravel associated rabies post exposure treatment in New South Wales residents, Australia, 2007e2011, a cross-sectional analysis. Travel Med Infect Dis 2013;11:421e6. Jentes ES, Blanton JD, Johnson KJ, Petersen BW, Lamias MJ, Robertson K, et al. The global availability of rabies immune globulin and rabies vaccine in clinics providing direct care to travelers. J Travel Med 2013;20:148e58. WHO. Current strategies for human rabies pre and postexposure prophylaxis. [WWW Document], n.d. WHO. URL http://www.who.int/rabies/human/WHO_strategy_prepost_ exposure/en/ [accessed 10.11.13].
Deborah Mills Travel Medicine Alliance Australia, GPO Box 2832, Brisbane 4001, Australia
E-mail address: [email protected]
16 October 2013
Available online at www.sciencedirect.com
ScienceDirect journal homepage: www.elsevierhealth.com/journals/tmid
EDITORIAL
Intradermal pre-exposure rabies vaccination. Promises and pitfalls KEYWORDS Intradermal rabies vaccine
In this special edition of Travel Medicine and Infectious Disease (TMAID), focusing on skin, it is timely to think about the intradermal (ID) rabies vaccine. Warrell published an excellent review of rabies vaccine in TMAID in 2012 [1]. The paper by Lau et al. [2] published in this issue of TMAID investigates the use of a different brand of rabies vaccine, using the modified intradermal regime published in 2011 with Human Diploid Cell Vaccine (HDCV) [3] The authors provide support for the efficacy of this regime when using Rabipur as opposed to HDCV. The use of ID rabies vaccine was described in 1976 [4], with the promise of allowing cheaper protection from a disease, which has been feared throughout history. Although deaths in travellers are rare (60 reported cases 1990e2012 [5]), rabies risk exposures are relatively common (2e13/1000 travellers per month, [6,7]). In travellers who are aware the horrors of this untreatable disease, a potential rabies exposure can be stressful, and cause major disruption to travel plans in the quest for appropriate treatment. The advice commonly given to travellers is “Your trip is short, so avoid petting dogs, and seek treatment if bitten” however this does not adequately deal with the issue of rabies prevention. “Trip is short” may initially sound plausible, but duration of trip is not a reliable defence against exposure. Rabies deaths have been observed in travellers after trips of two weeks or less [5]. The study [8] reported the mean time to injury was 15.3 days after departure from Australia and 88% were exposed within 30 days of arrival. “Avoid petting dogs” is potentially misleading to travellers. Geosentinel in 2007 reported [6] that dogs were responsible for only 51.3% of traveller’s exposures, and monkeys 21.2% (this was prior to the outbreak of rabies in
Bali.) Rabies exposures in travellers in two recent studies in Australia [8,9] reported 35.8% and 42% respectively were from dogs. Both studies noted more exposures from monkeys 49.4% and 45% respectively (especially in Bali). One could perhaps say “Avoid contact with mammals” however travellers may not have a choice. The mammals are sometimes the ones initiating contact. In study [8] in 40% of the exposed travellers, the mammal initiated the contact, and traveller initiated contact included activities like taking photos or shooing the animal. Most travellers would not perceive these as high risk animal interactions. In the NSW study published in this edition [9] the dog initiated contact in 38.0%. “Seek treatment if bitten” is a good plan in theory, but the difficulties of accessing proper post exposure treatment are twofold (finding a well trained provider with knowledge of current best practice, and finding the rabies immune globulin) and well described [10]. The paper by Kardamanidis et al. published in this edition concluded, “Opportunities for increasing pre-exposure treatment amongst individuals likely to be exposed should be promoted.” ID rabies vaccination provides this much needed opportunity for increasing pre-exposure treatment amongst individuals likely to be exposed. It also poses unique challenges to the practitioner: The recommendation of an off label vaccine, the storage of preservative-free, single dose rabies vaccine vials for multi-dose use, and the administration of the technically different intradermal technique, makes the ID option more suitable to larger travel clinics. Multidose ID regimes [2,3], have the advantage of decreasing the storage time required for single use vials used for ID courses. The occasional vaccinee who, for
1477-8939/$ - see front matter ª 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.tmaid.2013.10.007
336 no apparent reason, fails to generate an antibody level over the magic bar of 0.5 IU/ml, means that many travellers are subjected to blood tests in addition to their ID rabies course. To complicate matters, the level of 0.5 IU/ml is somewhat arbitrary and not a recognized correlate of protection. The criticism of rabies vaccine being especially expensive is fading. Costs of other vaccine are climbing to level of the rabies vaccine and more. The recommendation from the World Health Organisation that booster doses of rabies vaccines are not required [11] means pre-travel rabies vaccine is a long-term investment. ID vaccine is a useful solution to a niggling pre-travel problem. The tendency for travellers to present for their pretravel consultation closer and closer to their departure date adds a growing impetus for rapid pre-exposure rabies vaccination. Nirvana would perhaps involve one vial of IM rabies given ID in 4e8 sites, prior to sending the traveller on their merry way, safe in the knowledge of their adequate antibodies in 14 days. This has been used in some small studies [4] but as so often stated “further research is needed.”
Editorial
[4]
[5]
[6]
[7]
[8] [9]
[10]
Conflict of interest [11]
None declared.
References [1] Warrell MJ. Current rabies vaccines and prophylaxis schedules: preventing rabies before and after exposure. Travel Med Infect Dis 2012;10:1e15. [2] Lau Colleen L, Hohl Norman. Immunogenicity of a modified intradermal pre-exposure rabies vaccination schedule using a purified chick embryo cell vaccine. An observational study. Travel Med Infect Dis 2013;11:427e30. [3] Mills DJ, Lau CL, Fearnley EJ, Weinstein P. The immunogenicity of a modified intradermal pre-exposure rabies
vaccination ScheduledA case series of 420 travelers. J Travel Med 2011;18:327e32. Turner GS, Aoki FY, Nicholson KG, Tyrrell DA, Hill LE. Human diploid cell strain rabies vaccine. Rapid prophylactic immunisation of volunteers with small doses. Lancet 1976;1: 1379e81. Carrara P, Parola P, Brouqui P, Gautret P. Imported human rabies cases worldwide, 1990e2012. PLoS Negl Trop Dis 2013; 7:e2209. Gautret P, Schwartz E, Shaw M, Soula G, Gazin P, Delmont J, et al. Animal-associated injuries and related diseases among returned travellers: a review of the geoSentinel surveillance network. Vaccine 2007;25:2656e63. Piyaphanee W, Kittitrakul C, Lawpoolsri S, Gautret P, Kashino W, Tangkanakul W, et al. Risk of potentially rabid animal exposure among foreign travelers in southeast asia. PLoS Negl Trop Dis 2012;6:e1852. Mills DJ, Lau CL, Weinstein P. Animal bites and rabies exposure in Australian travellers. Med J Aust 2011;195. Kardamanidis K, Cashman P, Durrheim DN. Travel and nontravel associated rabies post exposure treatment in New South Wales residents, Australia, 2007e2011, a cross-sectional analysis. Travel Med Infect Dis 2013;11:421e6. Jentes ES, Blanton JD, Johnson KJ, Petersen BW, Lamias MJ, Robertson K, et al. The global availability of rabies immune globulin and rabies vaccine in clinics providing direct care to travelers. J Travel Med 2013;20:148e58. WHO. Current strategies for human rabies pre and postexposure prophylaxis. [WWW Document], n.d. WHO. URL http://www.who.int/rabies/human/WHO_strategy_prepost_ exposure/en/ [accessed 10.11.13].
Deborah Mills Travel Medicine Alliance Australia, GPO Box 2832, Brisbane 4001, Australia
E-mail address: [email protected]
16 October 2013
