The Global Availability of Rabies Immune Globulin and Rabies Vaccine in Clinics Providing Indirect Care to Travelers
We assessed rabies vaccine (RV) and immune globulin (RIG) availability on the local market by querying US Embassy medical staff worldwide. Of 112 responses, 23% were from West, Central, and East Africa. RV and RIG availability varied by region. Possible rabies exposures accounted for 2% of all travelers' health inquiries.
Rabies is an acute, fatal encephalomyelitis caused by neurotropic viruses (Family Rhabdoviridae, genus Lyssavirus); transmission to humans generally occurs from a rabid mammal bite. Rabies is preventable with prompt post-exposure prophylaxis (PEP), including proper wound care, rabies vaccine (RV) and, for previously unvaccinated individuals, rabies immune globulin (RIG). Currently, only two of the various RVs available worldwide are licensed in the United States for PEP or pre-exposure vaccination: purified chicken embryo cell and human diploid cell. Similarly, only human RIG (HRIG) is licensed in the United States, although other RIG, including equine RIG (ERIG), products are available worldwide.
The US Centers for Disease Control and Prevention (CDC) bases its rabies pre-exposure vaccination recommendations for US travelers on local rabies epidemiology and availability of rabies biologics for PEP at the traveler's destination. To better guide health recommendations, we sought to describe the accessibility and type of RIG and RV available to international travelers by surveying US Department of State Embassy medical officers and health unit staff (US Embassy medical staff) who provide health recommendations to US travelers overseas.
This survey was determined nonresearch by CDC Human Subjects Advisors. A web survey was conducted by distributing questions via e-mail to US Embassy medical staff that provide health advice, but not treatment, to travelers in country who call for health recommendations. For technical and privacy reasons, duplicate e-mails may have been sent to the same embassy.
This survey, called the Indirect Care Survey, was accessible from February 1 to March 30, 2011. This survey was done in tandem with the Direct Care Survey; however, Indirect Care Survey questions were directed to those providing advice rather than treatment. Two reminder e-mails were sent to encourage participation. For registration, respondents were asked their city, country, and an e-mail address. If more than one survey was started by respondents at the same embassy, the most complete survey was retained. If more than one survey was completed for an embassy, one survey was randomly selected. The survey contained approximately 20 questions, although count varied by participant's responses. Questions asked about the RIG and RV types used locally, the accessibility of these biologics for travelers' PEP, and where travelers were sent if biologics were not available. Respondents were asked to answer based on their experiences in 2010.
Region classifications from the Direct Care Survey were used. De-identified data were aggregated by region so that individual respondents could not be identified, and then analyzed using SAS 9.2 (SAS Institute, Cary, NC, USA).
The US Department of State estimated that approximately 200 surveys were distributed. Of 148 respondents, 36 were excluded owing to nonresponse or multiple responses. Of 112 analyzed responses, most came from West, Central, and East Africa (23%), Eastern Europe and Northern Asia (16%), and East and Southeast Asia (14%) (Table 1). Possible rabies exposures accounted for, on average, 2% of all travelers' health inquiries, but varied by region.
Selected results of the evaluation of the global availability of rabies immune globulin (RIG) and rabies vaccine (RV) for travelers: indirect care survey 2010*,•
Sixty-nine (68%) of 102 respondents stated RIG was available to travelers in the countries where they were stationed. Of these 69, 64 (93%) reported that RIG was available in the same city as the embassy and five (7%) did not provide information regarding referral locations. Of the 12 West, Central, and East Africa respondents, 58% reported RIG was sometimes, and 33% reported it was seldom or never, available (Table 1). Similarly, of the 12 East- and Southeast Asia respondents, 33% and 8% reported that RIG was sometimes, and seldom or never available, respectively. Overall, of 66 respondents, 37 (56%) reported HRIG use. Of these 37, 28 (76%) and 2 (5%) reported that an international pharmaceutical company or a local producer manufactured the HRIG, respectively.
Overall, 81 (82%) of 99 stated RV was available for travelers for PEP. Of these 81, 75 (93%) reported that RV was available in the same city as the embassy and the remaining 6 (7%) of 81 did not provide information regarding referral locations. Of 81 respondents, 69% reported that RV was often or always accessible for PEP (Table 1). The most commonly reported RV was Vero cell (30%). Vaccine produced by an international pharmaceutical company was reported by 22 (92%) of 24 reporting Vero cell vaccine use, 11 (58%) of 19 reporting human diploid cell vaccine, and 15 (68%) of 22 reporting purified chicken embryo cell vaccine.
When interpreting these data, several factors must be acknowledged. First, we surveyed the US Embassy medical staff, whose primary responsibilities are to provide medical care to embassy personnel; full ascertainment of local availability of RIG and RV was outside the scope of their normal work. The Direct Care Survey considered clinicians directly providing care to travelers, but was limited in geographic variation of responses. We attempted with this Indirect Care Survey to provide greater geographic variation. However, for privacy reasons, results were compiled into regions. This grouping limits the use in vaccine decisions for individual patients as countries within the regions differ. Also, for countries where rabies biologics are more difficult to locate, travelers may be more likely to call the embassy for guidance, leading to response bias. In addition, some travelers may contact health care professionals or hospitals, rather than the embassy. Finally, respondents reported about their experience in 2010 only, therefore our survey may not be representative of past, current, or future situations.
Recognizing these limitations, we found that inquiries regarding possible exposures to rabies accounted for, on average, 2% of all travelers' health inquiries. Our findings suggest that possible rabies exposures are a concern for travelers. It has been estimated from PEP records that 0.4% (range 0.01% to 2.3%) of travelers receive an at-risk bite per month of residence in a rabies-endemic country.
The percentage of rabies inquiries was higher in the Middle East and North Africa; Mexico, Central America, and the Caribbean; West, Central, and East Africa; and South Asian regions. These regions are mostly considered “high risk” by the World Health Organization (WHO), and both WHO and CDC recommend pre-exposure vaccination for travelers to these areas with likely contact with dogs or other vectors.[1, 5] A recent review of imported human rabies cases worldwide found that the places of exposure were in North and Sub-Saharan Africa, India, Southeast Asia, Central America, and Haiti.
Areas with greater risk, particularly West, Central, and East Africa; South Asia; and East- and Southeast Asia, also reported less access to RIG and RV. Travelers who experience a possible rabies exposure in these higher-risk areas will need to travel to a neighboring country/area or their home country to start or continue appropriate treatment. A change in the continuity of medical care may be detrimental to the patients as they may not have initially received adequate care, know what treatments were given at the origin of infection, or receive timely care.[6, 7]
Travel preparation should include a pre-travel medical consultation from a health care provider, 4 to 6 weeks before travel, especially if rabies pre-exposure vaccination is warranted. Providers should thoroughly discuss rabies in the traveler's customized health recommendations, including that the types of rabies biologics used abroad might differ from those in the United States and involve different routes, schedules of administration, and levels of quality and safety. Travelers should understand that the availability of rabies biologics abroad is ever-changing. HRIG is preferred for PEP, but it is expensive and often in limited supply. ERIG is often readily available; however, both its purified and unpurified forms have been reported with incidence of signs consistent with serum sickness. WHO recommends that appropriate precautions concerning anaphylaxis must be taken when ERIG is used. Providers should discuss with travelers the aforementioned consideration of vaccination, the avoidance of animals, proper actions should a possible rabies exposure occur, and the consideration of purchasing travel medical and evacuation insurance. Providers and travelers can find updated travel and country-specific recommendations at www.cdc.gov/travel.
The authors thank the health care providers and travelers at the US Department of State Embassies. The authors also acknowledge the contributions of Kevin Liske, Pauline Han, Michael E. Nesemann, Patrick Odenweller, Bethany Ullrich, Clive Brown, Mark Sotir, and Ava Navin.
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention (CDC).
Declaration of Interests
C.E.R. Research sponsorship was the following: During the past 2 years, travel support for participation in rabies seminars and research support for development of new rabies biologics via organizations that produce rabies products. The other authors state they have no conflicts of interest to declare.