Adequacy of Rabies Post-exposure Prophylaxis

By Lin H. Chen, MD, Assistant Clinical Professor, Harvard Medical School and Director, Travel Medicine Center, Mt. Auburn Hospital, Cambridge, MA, is Associate Editor for Infectious Disease Alert.

Dr. Chen has received research grants from the Centers for Disease Control and Prevention and Xcellerex.

Synopsis: Travelers who experience animal bites often also experience delays in obtaining post-exposure prophylaxis, especially delays in obtaining human rabies immune globulin [HRIG]. Some develop suboptimal post-vaccination rabies antibody titers. Pre-travel advice needs to address ways to avoid these potential risks for rabies after bites which occur while overseas.

Source: Uwanyiligira M, et al. Rabies post-exposure prophylaxis in routine practice in view of the new centers for disease control and prevention and world health organization recommendations. Clin Infect Dis 2012 Jul;55(2):201-5.

Uwanyiligira et al retrospectively analyzed charts of all patients seen at the Travel Clinic of the University Hospital in Lausanne, Switzerland, for rabies post-exposure prophylaxis (PEP) between January 2005 and August 2011. The study identified 110 patients, including 90 travellers. Their median age was 34 years (range, 2–79 years), and 53% were women. Of the 90 travelers with possible rabies exposure overseas, 54 sought evaluation at their destination, but 36 waited to obtain medical care until after return to Switzerland. Those who waited to obtain medical care in Switzerland had a median delay of 10 days (range 0-481 days) whereas those who started rabies PEP overseas had a median delay of 0 days (range 0-14 days).

All those who waited to initiate PEP in Switzerland received HRIG, but only 7/50 (14%) who initiated PEP overseas received HRIG. The countries where travelers received HRIG were Tunisia, Algeria, Thailand, Vietnam, Indonesia, and Brazil. However, HRIG administration was inconsistent in these countries because many other patients did not receive it.

There were 11 patients who received pre-exposure prophylaxis (PrEP) and rapid fluorescent focus inhibition tests (RFFIT) were done in these patients after the 2 post-exposure doses. Their geometric mean titer was 18.2 IU/ml (range 5.4-33.9 IU/ml). For 85 of the nonimmune patients, serology was obtained between 21-29 days after the 4th dose of rabies PEP. Their geometric mean titer was 3.7 IU/ml (range 0.1-38 IU/ml). Six of 90 previously unvaccinated patients had titers <0.5 IU/ml.

Commentary

The GeoSentinel Surveillance Network analysis of 23,509 ill travelers seen from January 1998–May 2005 found 1.4% of the records indicated animal injuries That required rabies PEP.1 The highest risk for exposure was travel to Asia (67% of cases), with Thailand, India, Indonesia, China, Nepal and Vietnam being leading countries where exposure occurred.1 Dogs were the main culprits (51%), followed by monkeys (21%) and cats (8%); the most common reason for travel was tourism.1 Most of the cases involved short-term travel: 12% travelled for <7 days, 53% travelled for <28 days, and 85% for <3 months, and their median trip duration was 23 days.1

Similarly, another study of 139 patients treated for possible rabies exposure at the Rabies PEP Service in the Liverpool School of Tropical Medicine from 2000 to 2009 found Thailand and Turkey to be the most common countries of exposure (22.3% of cases each).2 Dogs were also responsible for most bites (49.6%), and the majority of patients (63%) were aged 20-50 years.2 Only 3 of 78 (3.8%) of those needing rabies immunoglobulin (RIG) per UK guidelines received it while overseas and only 11 more patients received RIG on return to the UK; delay in care was also documented.2 Only 14 (10.1%) had received PrEP.2

Gautret et al reviewed 22 published rabies cases occurring travellers (tourists, expatriates and migrants) within the past decade, including 3 cases following short-term travel (≤2 weeks).3 Their review determined that expatriates were better vaccinated than tourists (31% vs. 12%) before travel.3 The risk of bite with potential rabies exposure is estimated at 0.4% of travelers per month of stay in a rabies-endemic country.3

A survey of German travel health advisors confirmed the emphasis on PrEP for expatriates where nearly all responders indicated that they would discuss the risk of rabies and preventive measures to long-term travelers and tourists planning to visit rural areas.4 However, only 35-60% of the advisors would provide this information to travellers on package tours or visiting urban centers or to business travelers.4 Clearly, improvement is needed in proper post-exposure management to persons who had PrEP as well as in reducing the inappropriate withholding of PEP in cases where treatment had been initially delayed.4

Uwanyilijira et al proposed measuring antibody levels on day 21 of the Essen PEP regimen to ascertain an adequate immune response. In an editorial, Wilde et al pointed out that few or no laboratories in rabies endemic countries can perform appropriate serology.5 Furthermore, failure to obtain PEP frequently is due to high cost of rabies vaccine and HRIG. Therefore, reducing the amount of rabies vaccine needed would contribute to better follow through with PEP, along with reducing the duration to initiation of PEP.5 They noted that modern high-quality equine rabies immune globulin produced in France, Thailand, China, and India are available in some rabies-endemic countries. This information is reassuring, though difficult in practice for travellers to determine the quality of the product they receive in endemic countries. Also, Uwanyilijira et al have shown the inconsistent use of rabies immune globulin in a number of countries.

This study has raised questions regarding adequacy of the reduced-dose Essen PEP with 4 doses of rabies vaccine, based on the suboptimal antibody levels (<0.5 IU/mL) in 6 of 90 patients (6.7%) following 4 doses. The authors have also identified the additional problems of delayed initiation of PEP in travelers who waited to obtain medical treatment after returning to Switzerland. Travellers should seek proper post-bite care as soon as possible and understand the importance of HRIG in addition to rabies vaccination.

References

  1. Gautret P, et al. GeoSentinel Surveillance Network. Animal-associated injuries and related diseases among returned travellers: a review of the GeoSentinel Surveillance Network. Vaccine. 2007 Mar 30;25(14):2656-63.
  2. Wijaya L, Ford L, Lalloo D. Rabies postexposure prophylaxis in a UK travel clinic: ten years' experience. J Travel Med 2011 Jul-Aug;18(4):257-61.
  3. Gautret P, Parola P. Rabies vaccination for international travelers. Vaccine 2012:5;30(2):126-33.
  4. Ross RS, Wolters B, Viazov SO, Roggendorf M. Awareness of rabies risks and knowledge about preventive measures among experienced German travel health advisors. J Travel Med 2006;13(5):261-7.
  5. Wilde H. Editorial Commentary: Rabies postexposure vaccination: are antibody responses adequate? Clin Infect Dis 2012;Jul;55(2):206-8.