BATS AND RABIEÍSWHAT RABIES PROPHYLAXISIS NEEDED AND WHEN?ATHANASIOS MICHOS, MD, PHD, AND THEOKLIS ZAOUTIS, MD, MSCE

There currently is no effective treatment for rabies, an almost alwaysfatal disease. Bats are increasingly being implicated as the principalwildlife reservoir for rabies transmission to humans. The best we cando is to aim for prevention by reducing the possibility of exposure andto apply prophylactic measures if exposure occurs.

R abies is a lethal disease caused by ribo-nucleic acid (RNA) viruses of the familyRhabdoviridae and genus Lyssavirus.^ This

worldwide zoonosis may infect all mammals, includ-ing humans. Eleven rabies species have been identi-fied, with all but 1 genotype being found in bats,'

Over the past 2 decades, hats have been reportedas the most frequent carriers of human rabies infec-tions in the United States,'

Among a notable number of human rabiespatients, a history of prior contact with bats was notelicited. As a result, postexposure prophylaxis forsuch patients was not provided,^ ''

Exposure to the clinically ill mammal carrieroccurs most often through a bite or scratch. Theincubation period of lyssaviruses may range fromdays to several years but is most frequently between2 and 12 weeks,'* The virus then enters the central

nervous system and causes acute encephalomyelitis,which is almost always fatal (Eigure 1)," '

Reliably effective treatment of rabies is not cur-rently available. As a result, the primary means foraverting deaths attributed to rabies is through pro-phylactic measures.

Prevention of the disease in man is possible byreducing the probability of exposure to the virus frompotentially rabid animals, as well as through the appli-cation of preexposure and postexposure strategies,"

Annually, 16,000 to 39,000 people in the UnitedStates are potentially exposed to rabies and receiveeffective postexposure prophylaxis (PEP) to deterthe development of rabies,''

The direct cost of PEP is estimated to be around$2,500, and treatment is often administeredunnecessarily,''"

After the effective prevention of canine rabies

is a lecturer in pédiatrie infectious diseases, 1st Department of Pediatrics, University of Athens, Athens, Greece, '^ '^ ' ' * / > " T T Sis associate professor of pediatrics and of epidemiology. University of Pennsylvania School of Medicine, Philadelphia, and associate chief, Division ofInfectious Diseases, the Children's Hospital of Philadelphia. The authors have nothing to disclose in regard to affiliations VKith, or financial interestsin, any organization that may have an interest in any part of this article.

46 CONTEMPORARY PEDIATRICS OCTOBER 2011

»BATS AND RABIES

Rabies bite wound

Incubation period(5d to <2 yr)

Prodrome(0-1 Od)

Malaise, anorexia, irritability, low-grade fever,paresthesia, pain, numbness at the bite site.

Acute neurologic signs(2-7 d)

Dysarthria, dysphagia, excessive salivation,diplopia, vertigo, agitation, visual or auditoryhallucinations, manic behavior alternating withlethargy, hydrophobia, polyneuritis.

Coma(5-14d)

Hydrophobia, prolonged apnea, generalizedflaccid paralysis, seizures, coma with ultimaterespiratory and vascular collapse.

DEATH

FIGURE 1 ^

Clinical stages of rabies infection. Information from RupprechtCE, et ai'

in the United States, the primary maintenanceof rabies virus has been among wildlife species.'Over the past 2 decades, the majority of naturallyacquired, indigenous human rabies cases in theUnited States were primarily associated with expo-sure to rabid bats."'^

Bats and rabiesBats constitute the sole mammalian species with theability to fly. In excess of 1,100 species of bats have

been documented globally."More than 30 rabies-infected

bat species have been reportedin the United States, with mul-tiple viral lineages associatedwith different bat species.'''Rabid bats are increasinglyimplicated as the principalwildlife reservoir for rabiestransmission to humans.

Subclinical rabies infectionshave been described amongseveral bat species worldwide.^Viral RNA has been detected

in the saliva, blood, and various organs of healthybats captured in field colonies"; however, most cases

Points Taken

• 16,000 to39,000 peopleper year may beexposed to rabies.

Q 34 humancases of rabiesassociatedwith bats werereported in theUnited States in1990-2007.

detected so far have been ineither diseased or deceasedanimals.

Moreover, experimen-tal infection of bats withrabies most often leads toshort excretion and rapiddeath."*'^ The rabies virusis inactivated by desiccationand ultraviolet irradiation,and it does not persist out-side the infected animal.'

Bat rabies virus variantsassociated with silver-hairedbats {Lasionycteris noctiva-gans) and eastern pipistrelles{Pipistrellus subflavus) havebiologic characteristics thatmight allow for an elevatedlikelihood of infection aftersuperficial inoculation,

including infection of epidermal cells."*"

Although bats described as having aggression,ataxia, disorientation, or lethargy are significantlymore likely to have rabies than those with none ofthese signs, bats found dead are no more likely tohave rabies than those reported alive before submis-sion for examination.'^

Rabies is reported in less than 1% of free-rangingbats and is diagnosed in 5% to 15% of bats submittedfor public health evaluation."

Epidemiology of bat rabiesFrom 1990 to 2007, 34 human rabies cases associ-ated with bats were reported in the United States.'Bite or contact with a bat was reported in the minor-ity of cases (6 and 2, respectively), whereas no bitebut possible physical contact was reported in15 cases (presence of a bat in home or workplace or inthe room where the person had been sleeping).

In 11 cases, no encounter with a bat was reported. Inthese cases, after matching the genetic sequences ofthehuman rabies viruses with those of bats, the most plau-sible hypothesis is that an unreported or undetected batbite had occurred.

Clustering of human cases associated with bat expo-sures within the same family, group, or community has

48 CONTEMPORARY PEDIATRICS OCTOBER 2011

»BATS AND RABIES

never been reported in the United States,'"-'"A decrease in the absolute number of reported

rabid bats was noted during 2009,''' The propor-tion of bats submitted for testing that were rabiddecreased from 5,9% in 2008 to 5,8% in 2009, Rabidbats were reported in all 48 contiguous states. Eightstates (Idaho, Illinois, Indiana, Mississippi, Nevada,Oregon, Utah, and Washington) reported rabiesonly in bats,

A 50% or higher increase in the number of rabidbats was reported in 8 states (Arkansas, Indiana,Maryland, North Carolina, New Hampshire, NewMexico, Oklahoma, and West Virginia), No humanrabies eases were reported during the first 7 months

Most states have a rabies hotline to get informa-tion ahout exposures and treatment. Contact detailsfor state and local consultation offices are availableonline (www,cdc,gov/rabies/resources/contacts,html).

Who needs postexposureprophylaxis after bat contact?The necessity of postexposure prophylaxis for rabiesafter bat contact poses special challenges. Exposurescould oeeur in circumstances considered otherwisenegligible because of the limited injury inflicted bythe bat.

Transmission of bat rabies virus can occur fromminor and/or underappreciated or unrecognizedbites or lesions. In human rahies eases thought tobe of bat origin in the United States, 60% of eases inthe 1990s and 17% of eases after 2000 did not reporta bat bite,'"* This may be attributed to the limitedbite size inflieted, laek of realization of previous batexposure, and/or a reeall bias secondary to the man-ifestation of rabies," For these reasons, any directexposure to a bat should be evaluated for a potentialexposure to rabies.

If it is feasible, bats involved in potential humanexposures should be submitted for rabies diagnosisto speeialized laboratories in a timely and seeuremanner. If it is deemed that the bat is not rabid, asin most eases of surveyed bats (approximately 94%),there is no need for further investigations or postex-posure prophylaxis,'"

The Advisory Committee on ImmunizationPractices of the Centers for Disease Control and

Points Taken

• 6096 of ushuman rabies casesin the 1990s and17% of cases after2000 did not reporta bat bite.

• ACIP has maderecommendationsregarding theevaluation ofpersons with directcontact with bats.

Prevention has made recommendations regardingrahies exposure evaluation of persons with directcontact with bats, as well as persons who may havehad an unacknowledged contact with bats,''

Direct contact is definedas bite, scratch, and/ormucous membrane exposure(abrasions, open wounds)with a bat.

Indirect contact includesthose situations in whicha deeply sleeping personawakens to find a bat in theroom, an adult witnesses anunattended child sleeping ina room with a bat, or a men-tally disabled or intoxicatedperson finds a bat in a room.

If a person can be reason-ably certain that a bite, a scratch, or mucous mem-hrane contact did not occur, or the bat is availablefor testing and is negative for the presence of rabiesvirus after laboratory evaluation, PEP is not neces-sary (Table 1),' In more complex situations in whichthere is doubt about the type of exposure, consulta-tion with either an infectious diseases specialistor local health department professional should besought,

GSIIQ When to give prophylaxisafter bat exposure

Give prophylaxis

Bat is not available and there is• Certain contact

- Bite- Scratch- Mucous membrane contact

• Possible contact- Deeply sleeping person awakens to find a bat

in the room- Adult witnesses a bat in the room of a previously

unattended child or a mentally disabled orintoxicated person

Do not give prophylaxis

• Bat testing is negative for rabies• Reasonable certainty from an aware person of no

possible contact

Information from Manning SE, et al,'

C o n t e m p o r a r y P e d i a t r i c s . c o m OCTOBER 2011 CONTEMPORARY PEDIATRICS 51

BATS AND RABIES

What type of postexposureprophylaxis is appropriate?Postexposure prophylaxis for the prevention ofrabies in humans exposed to the rabies virus shouldbe given as soon as possible and includes 3 steps:1) prompt and thorough wound cleansing, 2) passivevaccination with human rabies immune globulin(HRIG), and 3) vaccination with cell culture rabiesvaccines (Table 2; Figure 2).^" This combined pro-phylaxis has been found uniformly effective whenappropriately administered.

When a documented or likely bat exposure hasoccurred, postexposure prophylaxis should beadministered regardless of the length of the delaybecause the incubation period may extend overseveral years. In a person who already has clinicalsigns compatible with rabies, the administration ofpostexposure prophylaxis has been demonstrated tobe consistently ineffective.'"

The combination of HRIG and vaccine is rec-ommended for both bite and nonbite exposuresreported by persons who have never been previ-ously vaccinated for rabies, regardless of the intervalbetween exposure and initiation of prophylaxis. Ifpostexposure prophylaxis has been initiated andappropriate laboratory diagnostic testing (ie, thedirect fluorescent antibody test) indicates that the

exposing animal is not rabid, postexposure prophy-laxis may be discontinued.

Because of the potential consequences of inad-equately managed rabies exposure, pregnancy isnot considered a contraindication to postexposureprophylaxis.

TREATMENT OF WOUNDS

Wound cleansing is especially important in rabiesprevention because thorough wound cleansing alonewithout other postexposure prophylaxis had beenshown to reduce the likelihood of rabies in animalstudies.

Immediate gentle irrigation with water or a dilutewater-povidone-iodine solution should be per-formed with special care so as not to damage skin ortissues (Table 2).'"

RABIES IMMUNE GLOBULIN

Use of rabies immune globulin (RIG) provides arapid, passive immunity that extends over a limitedtime period because the RIG half-life approximates21 days.' Two antirabies immune globulin (IgG) for-mulations prepared from hyperimmunized humandonors have been licensed and are currently availablein the United States (Table 3).' It is recommended thatHRIG should be administered concurrently with the

Rabies postexposure prophylaxis schedule—United States 2010

Intervention Regimen

Wound Immediate, thorough cleansing of all wounds with soap and water. If available, a virueidalcleansing agent (eg, povidone-iodine solution) should be used to irrigate the wounds.

Administer 20 lU/kg body weight. If anatomically feasible, the full dose should be infiltratedaround and into the wound(s), and any remaining volume should be administered atan anatomieal site (IM) distant from vaecine administration. Also, HRIG should not beadministered in the same syringe as vaccine. Because RIG might partially suppress activeproduction of rabies virus antibody, no more than the recommended dose should beadministered.

Human diploid cell vaccine or purified chick embryo cell vaccine 1.0 mL, IM (deltoid area),*4 doses (1 each on days 0, 3, 7 and 14)'' for immunoeompetent persons.

Abbreviations: HRIG, buman rabies immune globulin; IM, intramuscular; RIG, rabies immune globulin.a. The deltoid area is the only acceptable site of vaccination for adults and older children. For younger children, the outer aspect of the thigh may

be used. Vaccine should never be administered in the gluteal area.b. For persons with immunosuppression, rabies postexposure prophylaxis should be administered using all 5 doses of vaccine on days 0,3, 7,14,

and 28.Information from Rupprecht CE, et,' and Committee on Infectious Diseases."

HRiG

Vaccine

52 CONTEMPORARY PEDIATRICS OCTOBER 2011

»BATS AND RABIES

1 , Thorough cleansing of the wound2. Vaccination (4 doses at 0,3,7, and 14 d intramuscularly)

3, Rabies immunoglobulin (time 0): 20 lU/Kgintramuscularly at different site from the vaccine

FIGURE 2

Postexposure prophylaxis regimen for rabies. Information

from Committee on Infectious Diseases."

first vaccine dose in all postexposure prophylaxis regimenswith the exception of previously vaccinated individuals,

HRIG is administered only once (ie, at the initiation ofantirabies prophylaetie treatment) to previously unvaeci-nated individuals in order to provide immediate, passive,rabies virus-neutralizing antibody coverage until thepatient responds to human diploid cell vaccine (HDCV)or purified ehiek embryo cell vaccine (PCECV) byactively producing antibodies,' If not administered con-currently with the vaccine, HRIG may be administeredthrough the seventh day of the postexposure prophy-laxis treatments. Beyond this time, the administrationof HRIG is not recommended, because an antibodyresponse to the cell culture vaccine is presumed to haveoccurred,' Because HRIG can partially suppress activeantibody production, the administered dose should notexceed the recommended dose of HRIG (20 IU/kg for allage groups).

If it is anatomically feasible, the full dose of HRIGshould be thoroughly infiltrated in those areas aroundand into the wounds. Any remaining volume should heinjected intramuscularly (IM) at a site distant from thatof the vaccine administration, HRIG should never beadministered in the same syringe or in the same anatomicsite as the first vaeeine dose. However, subsequent dosesof the vaeeine in the 4-dose series ean be administeredin the same anatomic location where the HRIG dose wasadministered, should this be the preferable site for vaccineadministration (ie, deltoid for adults or anterolateral thighfor infants and young children),^"

C o n t e m p o r a r y P e d i a t r i c s , c o m

STATEMENT OF OWNERSHIP,MANAGEMENT, AND CIRCULATION

(Requester Publications Only)(Required by 39 use 3685)

1. Publication Title: Contemporarv Pediatrics

2, Publication Number: 8750-0507

}. Filing Date: 9/?0/l 1

4, Issue Frequency: Monthly

5, Number of Issues Published Annually: 12

e. Annual Subscription Price (if any): $89 00

7. Complete Mailing Address of Known Office of Publication:

1Î1 West First Street, Duluth, St. Louis County, Minnesota 55802-2065Contact Person: Knstina BildeauxTelephone: 507-895-6758

8. Complete Mailing Address of Headquarters or Ceneral Business Office of Publisher

a o i Colorado Avenue, Suite 280, Santa Monica, CA 90404

9. Full Names and Complete Mailing Addresses ofGroup Publisher: Ken Sylwa, 485 Route 1 South Building F, 1st Floor Iselin, NJ 08830

Publisher: Samintha Armstrong, 485 Route 1 South Building F, 1 st Floor Iselin, NJ 08830

Senior Editor Kathy Method, Great Northern Corporate Center II, 24950 Country Club Blvd, North

Olmsted, OH 44070

10. This publication is owned by: Advanstar Communications Inc., 2501 Colorado Avenue, Su e 280,Santa Monica, C/i 90404. The sole shareholder of Advanstar Communications Inc is: Advanstar, Inc,whose mailing address is 2501 Colorado Avenue, Suie 280, Santa Monrca, CA 90404

11. Advanstar Communications Inc is a borrower under Cr«dK Agreements dated May 11,2007, with various lenders as named therein from time to time. As of lune 16, 2011,the agent for the lenders is: Credit Suisse, Administrative Agent Eleven MadisonAvenue, New York, NY 10010. Advanstar Communications Inc is a borrower underan agreement with VSS-AHC Holdings, U C , 350 Park Avenue, New York, NY 10022

12. Does Not Apply

13. Publication Title: Contemporary Pediatrics

14. Issue Date for Circulation Data Below: August 2011

15. Extent and Nature of Circulation

A. Total Number o! Copies

B. Legitimate Paid and/or Requested Distribution

Average No.Copies Each

Issue DuringPreceding12 Months

52,201

No. Copies ofSingle Issue

PublishedNearest toFiling Date

53,341

1, Outside County Paid/Requested Mail

Subscnptions Stated on PS Form 3541

2, In-County Paid/Requested Mail SubscriptionsStated on PS Form 3541

3. Sales Through Dealers and Carriers, StreetVendors, Counter Sales, and Other Paid orRequested Distnbution Outside USPS

4. Requested Copies Distnbuted by Other MailClasses Through the USPS

C. Total Paid and/or Requested Circulation(Sum of /51> (I), (2). ß). and (4)

29,760 31,305

29,788 31,332

D. Non-requested Distnbution

1. Outside County Non-requested

Copies as Stated on PS Form 3541

2, In-County Non-requested

Copies Stated on PS Form 3541

3. Non-requested Copies Distributed Throughthe USPS by Other Classes of Mail

4, Non-requested Copies Distributed

Outside the Mail

E. Total Non-requested Distribution(Sum of I5d (1), (2), (5) and (4»

f. Total Distribution (Sam oi IScande)

C. Copies not Distributed

H, Total (Sum of 15f and g)

1, Percent Paid and/or Requested Circulation

21,947

191

22,138

51,926

275

52,201

57,37*

21,551

251

2 U 0 2

53,134

207

53,341

58.97%

16. Publication for a Requester Publication is required. Will be printed in the

October issue of this publication

17, Name and Title of Editor, Publishers, Business Manager, or Owner:Christine Shappell, Audience Development Director

Signature:

Date: 9/29/11I certify that the statements made by me above are correct and complete.

CONTEMPORARY PEDIATRICS 53

»BATS AND RABIES

Rabies biologic products availablein the United States

Product

Rabies immuneglobulin'

Human rabiesvaccine

20IU/Kg Local

Human diploid eellvaccine 1 mL Intramuscular

Purified ehiekembryo cell vaeeine

a. As much of the product as is anatomically feasible should be infiltrated into and around thewound. Any remaining product should be administered intramuscularly in the deltoid or quadriceps(at a location other than that used for vaccine inoculation to minimize potential interference).Information from Manning SE, et al.'

VACCINATION

Initially, guidelines for vaccination schedules rec-ommended 5 doses for immunoeompetent patients.However, recently it was recommended that thenumber of vaccine doses be reduced to 4.' Thispolicy was also endorsed by the American Academyof Pediatrics."

The first dose of the 4-dose vaccination scheduleshould be administered as soon as possible afterexposure (Table 2, Figure 2).^" This date is identi-fied as day 0 of the postexposure prophylaxis series.Additional doses should then be administered ondays 3, 7, and 14 after the initial vaccination date.

For immunosuppressed persons, an additionalfifth dose should be administered on day 28.

Immunosuppressive agentsshould not be administeredduring postexposure prophy-laxis unless they are essentialfor the treatment of other con-comitant conditions.'

Two rabies vaccines areavailable for use in the UnitedStates (Table 3)' and can beadministered in conjunctionwith HRIG at the beginning ofpostexposure prophylaxis.

Among adults and olderchildren, the vaccine shouldalways be administered IM in

the deltoid area, whereas among children, it may bealso administered in the anterolateral aspect of thethigh if preferred.^" The gluteal area should never

Points Taken

• Two rabiesvaccines areavailable for use inthe United Statesand can be givenin conjunction withHRIG.

• Once started,rabies prophylaxisshould not beinterrupted ordiscontinued.

be used for HDCV or PCECV injectionsbecause administration of HDCV in this arearesults in lower neutralizing-antibody titers.

Dose Route Rabies vaccines induce an active immuneresponse that includes the production ofvirus-neutralizing antibodies.

The active antibody response requiresapproximately 7 to 10 days to develop, and

1 mL Intramuscular detectable rabies virus-neutralizing antibod-ies generally persist for several years thereaf-ter.^ A vaccination series is usually initiatedand completed with 1 vaccine product.

Once vaccination has been initiated, delaysof a few days longer than the recommended

interval are not thought to reduce effectiveness.'However, the po ten t i a l effect of delays in vac-cine dose adminis t ra t ion extending several weeksremains unknown.

For most cases with minor deviations from theoriginal vaccination schedule, vaccine doses maybe administered as though the patient were onschedule.

No testing of patients completing preexpo-sure or postexposure prophylaxis is necessary todocument seroconversion unless the person isimmunosuppressed.

Once initiated, rabies prophylaxis should not beinterrupted or discontinued because of local or mildsystemic adverse reactions to the rabies vaccine.

The HDCV used in Canada and the United Stateshas been associated with allergic reactions (11 casesper 10,000 vaccinated persons, 9 of which weretype 1 anaphylactic reactions).' Usually such reac-tions can be successfully managed with epinephrineadministration. When a person with a history ofsevere reactions to the rabies vaccine must be revac-cinated, empiric intervention, including pretreat-ment with antihistamines, may be considered.

Prevention strategyRabies is associated with the highest case-fatalityratio among infectious diseases. Rabies control inbats by conventional methods is not currently feasi-ble.' Prevention of human rabies infection from batrabies virus continues to be dependent on carefulassessment of exposed persons and judicial admin-istration of postexposure prophylaxis. SI

54 CONTEMPORARY PEOIATRICS OCTOBER 2011

BATS AND RABIES

R E F E R E N C E S

1 . Manning SE, Rupprecht CE, Eishbein D, et al; Advisory Committee on

Immunization Practices Centers for Disease Control and Prevention

(CDC). Human rabies prevention—United States, 2008: recommenda-

tions of the Advisory Committee on Immunization Practices. MMWR

Recomm Rep. 2008;57(RR-3):l-28.

2 . Megali A, Yannic G, Zahno ML, et al. Surveillance for European bat lys-

savirus in Swiss bats, Arcti Virol. 2010;155(10):1655-1662.

3. De Serres G, Sl<owronsi<i DM, Mimauit P, Ouakki M, Maranda-Aubut

R, Duval B. Bats in the bedroom, bats in the belfry: reanalysis of

the rationale for rabies postexposure prophylaxis. Clin Infect Dis.

2009;48(ll):1493-1499,

4 . De Serres G, Dailaire E, Côte M, Skovïronski DM. Bat rabies in the

United States and Canada from 1950 through 2007: human cases viíith

and without bat contact. Gin Infect Dis. 2008;46(9):1329-1337.

5. Hemachudba T. Human rabies: clinicai aspects, pathogenesis, and

potential therapy. Curr Top Microbiol Immunol. 1994;187:12H43.

6 . Nel LH, Markotter W. Lyssaviruses. Crit Rev Microbiol.

2007;33(4):301-324,

7. Rupprecht CE, Briggs D, Brown CM, et al; Centers for Disease Control

and Prevention (CDC). Use of a reduced (4-dose) vaccine schedule for

postexposure prophylaxis to prevent human rabies: recommendations

of the advisory committee on immunization practices. MMWR Recomm

Rep. 2010;59(RR-2):l-9.

8 . Rupprecht CE, Gibbons RV. Clinical practice. Prophylaxis against

rabies. NEnglJMed 2004;351(25):2626-2635.

9. Vaidya SA, Manning SE, Dhankhar P, et al. Estimating the risk of rabies

transmission to humans in the U.S.: a Delphi analysis. BMC Public

Heaitt). 2010;10:278.

10. Moran GJ, Talan DA, Mower W, et aL Appropriateness of rabies

postexposure prophylaxis treatment for animal exposures. Emergency

ID Net Study Group. JAMA. 2000;284(8):1001-1007.

1 1 . Committee on Infectious Diseases. Rabies-prevention policy update:

new reduced-dose schedule. Pediatrics. 2011;127(4):/85-787.

12. Wang X, DeMaria A, Smole S, Brown CM, Han L. Bat rabies in

Massachusetts, USA, 1985-2009. Emerg Infect Dis. 2010;16(8):1285-1288.

13. Eooks AR, Brookes SM, Johnson N, McElhinney LM, Hutson AM.

European bat lyssaviruses: an emerging zoonosis. Epidemiol Infect.

2003;131(3):1029-1039.

14. Blanton JD, Palmer D, Rupprecht CE. Rabies surveillance in the United

States during 2009. JAm VetMedAssoc. 2010;237(6):646-657.

15. Amengual B, Whitby JE, King A, Cobo JS, Bourhy H. Evolution of

European bat lyssaviruses. J Gen Virol. 1997;78(Pt 9):2319-2328.

16. Kirkbride H, Brown K, Morgan D, Larkin L. Rabies risk from contact

with bats. VetRec. 2008;163(16):491.

17. Warrell MJ, Warreii DA. Rabies and other iyssavirus diseases. Lancet

2004;363(9413):959-969. Erratum in: tancet 2004;364(9451):2096.

18 . Calisher CH, Childs JE, Eield HE, Holmes KV, Schountz T. Bats:

important reservoir hosts of emerging viruses. Clin Microbiol Rev.

2006;19(3):531-545.

19. Messenger SL, Smith JS, Rupprecht CE. Emerging epidemiology of bat-

associated cryptic cases of rabies in humans in the United States. Clin

Infect Dis. 2002;35(6):738-74Z

2 0 . Mondul AM, Krebs JW, Childs JE. Trends in national surveillance for

rabies among bats in the United States (1993-2000). J Am Vet Med

Assoc. 2003;222(5):633-639.

2 1 . Blanton JD, Robertson K, Palmer D, Rupprecht CE. Rabies sur-

veillance in the united States during 2008. J Am Vet Med Assoc.

2009;235(6):676-689.

2 2 . Rupprecht CE, Hanlon CA, Hemachudha T, Rabies re-examined. Lancet

7nfecfD/s. 2002;2(6):327-343.

C" Gebauer

Patient ComfortS O L U T I O N S '

C'Otbauer Company

Less Painful Injections InstantlyGebauer's Pain Ease® Topical AnestheticSkin RefrigerantChildren do not need to experience the pain associated

with the increasing number of injections. Gebauer's

Pain Ease non-drug topical anesthetic skin refrigerant

spray is fast, easy, and safe. Gebauer's Pain Ease,

unlike other topical anesthetics containing lidocaine,

prilocaine, or benzocaine, is not absorbed into the blood

stream and there is no systemtic toxicity. No waiting

as with anesthetic creams. No prescription to write

for each patient. Just spray 4 to 10 seconds prior to

immunizations, injections, venipunctures, IV placement,

and minor surgical procedures for immediate anesthetic

effect. Approved for use on minor open wounds and

intact oral mucous membranes. Temporary numbing

lasts approximately one minute and can be reapplied as

needed. Nonflammable. Mist and Medium Stream Sprays.

Important Risk and Safety InformationPublished clinical trials support the use in children

three years of age and older

Do not use on large areas of damaged skin, puncture

wounds, animal bites or serious wounds

Do not spray in eyes

Over spraying may cause frostbite

Freezing may alter skin pigmentation

Use caution when using product on diabetics or

persons with poor circulation

Apply only to intact oral mucous membranes

Do not use on genital mucous membranes

The thawing process may be painful and freezing may

lower resistance to infection and delay healing

If skin irritation develops, discontinue use

Rx only

Gebauer CompanyThe Mosf Trusted Name In Skin

Refrigerants For Over 100 Years!'

800.321.9348 • www.GebauersPainEase.com/cp

Copyright of Contemporary Pediatrics is the property of Advanstar Communications Inc. and its content may

not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written

permission. However, users may print, download, or email articles for individual use.